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First published online 4 July 2007
doi: 10.1242/dev.003764
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Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.
* Author for correspondence (e-mail: fuller{at}cmgm.stanford.edu)
Accepted 12 May 2007
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SUMMARY |
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 TOP SUMMARY INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Key words: Translational control, eIF4G, Cell cycle, Meiosis, Spermatocyte, Drosophila
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INTRODUCTION |
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TOPSUMMARYINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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;
Kuersten and Goodwin, 2003).
Likewise in spermiogenesis, in which drastic remodeling of the cell continues
after transcription is largely shut down, key mRNAs are initially
translationally repressed, then actively translated at specific times in the
differentiation sequence (Giorgini et al.,
2002; Hempel et al.,
2006; Schafer et al.,
1990). A third striking case is the specialized cell cycle of
meiosis. In vertebrate oocytes arrested in meiotic prophase, large numbers of
mRNAs required for subsequent oocyte maturation and early embryogenesis are
present but translationally silent. Resumption of meiosis is triggered by
physiological signals that initiate a cascade of stepwise translation of
selected mRNAs that drives meiotic cell cycle progression. Emerging evidence
suggests that distinct mechanisms of translational repression and activation
act on specific mRNAs at different steps in the process (reviewed in
Vasudevan et al., 2006).
A key regulatory point for translational control in eukaryotes is
initiation, instigated by binding of the translational initiation complex to
the 5' cap of the mRNA, leading to recruitment of the ribosomal
subunits. Components of the translation initiation complex are conserved
across eukaryotes. The eIF4E subunit binds the 5' cap, the RNA helicase
eIF4A is believed to unwind secondary structure in the 5' UTR, and eIF4G
serves as a crucial scaffold to bring those two proteins together. eIF4G also
binds an additional key regulator of translation initiation, poly(A)-binding
protein (PABP) (Tarun and Sachs,
1996).
An important outstanding question for how sequential developmental events can be ordered by translational control is how the translation initiation machinery can become targeted to and activated at specific subsets of mRNAs, and how this machinery might change in different cell types and stages. Here we show that eIF4G2, a novel homolog of the core translation initiation complex scaffold protein eIF4G, is required for meiotic cell cycle progression and normal spermatid differentiation during male gamete differentiation in Drosophila. The requirement for eIF4G2 is cell type- and stage-specific: strong loss-of-function mutants are male sterile but viable and female fertile. We found that eIF4G2 is required for the normal stage-specific expression of cell cycle regulatory proteins in spermatocytes and for many aspects of spermatid differentiation.
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MATERIALS AND METHODS |
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TOPSUMMARYINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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).
The nc32 and XM alleles were identified in a screen for
mutants that failed to complement ß2-tubulin mutation(s)
(Fuller, 1986).
Z3-3283 and BR21-37 were identified in screens for viable
but male sterile mutations by Wakimoto et al.
(Wakimoto et al., 2004) and
Elizabeth Raff (Indiana University, Bloomington, IN), respectively, and the
four mutants were shown to be allelic by complementation. The following
combinations of eIF4G2 alleles tested showed an equally severe mutant
phenotype: nc32/Df(3R)mbc1, nc32/XM, XM/BR21-37, BR21-37/Z3-3283 and
nc32/BR21-37. The nc32 allele was initially located by
recombination mapping in the region between hh and Pr on 3R
(Fuller, 1986).
Df(3R)mbc1 and Df(3R)Exel9014 did not complement
nc32, whereas Df(3R)Exel6194 and Df(3R)crb-F89-4
complemented nc32, placing the locus in polytene interval
95A5-7;95D6-11. For sequencing each of the four alleles, genomic DNA was
extracted from flies carrying that allele over Df(3R)mbc1. In the
text and figures, all eIF4G2 homozygous mutants shown were
BR21-37/Z3-3283.
The twe-lacZ reporter is as previously described
(White-Cooper et al., 1998).
The original Dj-GFP reporter line (on chromosome 3) was generated in
the Renkawitz-Pohl laboratory (Santel et
al., 1997) and was obtained (for ease of shipping) from the
laboratory of Craig Montell (Johns Hopkins University, Baltimore, MD). The
transgene was hopped off of the third chromosome by crossing in transposase
and selecting for transpositions off the third.
Histology
Phase-Hoechst staining was performed as described in Lin et al.
(Lin et al., 1996), and in
situ hybridization as in Hiller et al.
(Hiller et al., 2001).
Anti-Cyclin B (CycB) (1:10, F2F4; BD Biosciences) and anti-tubulin (1:200,
DM1A; Sigma) immunostaining was performed using methanol/acetone fixation as
in Glover and Gonzalez (Glover and
Gonzalez, 1993). Anti-Fzo [1:700, rabbit polyclonal
(Hales and Fuller, 1997)] and
anti-HA (1:1000, 16B12; Covance) immunostaining was performed using
ethanol/formaldehyde fixation as in Hime et al.
(Hime et al., 1996).
ß-galactosidase activity assays and in situ hybridization were performed
as in White-Cooper et al. (White-Cooper et
al., 1998).
Cloning
Our cDNA clone for a portion of the 5' half of the eIF4G2
coding sequence, amplified from testis RNA, represented a different splice
isoform from the annotated sequence in FlyBase. In particular, the sequence
corresponding to bases 1318 to 1434 of the original annotated coding sequence
was spliced out; thus, the protein sequence encoded by this testis transcript
did not include the 39 amino acids VCKR...NSTLTQ. All amino acid numberings in
this paper reflect the sequence of this cDNA clone, which was used for making
the tagged protein for expression in S2 cells. This splice form was also
identified in the accompanying paper
(Franklin-Dumont et al.,
2007).
The rescue construct consisted of genomic DNA from 2221 bp 5' of the
ATG, 6718 bp of protein coding sequence plus introns, 703 bp downstream of the
stop codon, and an SV40 terminator. The first three were PCR-amplified from
genomic DNA, with the following restriction sites added in the primers:
NotI/XbaI (5' region), XbaI/EcoRV
(coding sequence plus introns), EcoRV/XhoI (3'
region). All three were subcloned and sequenced for mutations. The SV40
terminator was PCR-amplified from pFAF
(Chen and Fischer, 2002), with
SalI/XhoI sites added to the ends of the primers. The
transgene was assembled sequentially into pBS-KS+, then moved into pCASPER4
using NotI/XhoI. To generate an HA-tagged eIF4G2 reporter
protein, we added 3xHA (PCR-amplified with SpeI/XbaI sites
added in primers) to the N-terminus, by inserting the 3xHA fragment into the
XbaI site of the rescue construct just upstream of and in frame with
the AUG.
Templates for eIF4G2, eIF4G and twine in situ probes were
generated by PCR from genomic DNA, then cloned into pCRII-TOPO (Invitrogen).
The following primers were used: for eIF4G,
5'-GGATCAACACCGATATCCAGA-3' and
5'-GGTTGTATACGTGAGGCCTT-3'; for eIF4G2,
5'-AACCGTTCCCGAGGTACATC-3' and
5'-TCACCGTAGACTTGTGCA-3'; for twine,
5'-GCCAATAAAGTTGACCGCA-3' and
5'-ATGCCGCTTCAGCATCCATT-3'. The cycB cDNA was used as a
probe template, as in White-Cooper et al.
(White-Cooper et al.,
1998).
To generate the tagged protein constructs for expression in S2 cells, the
eIF4G2 protein coding sequence was amplified in three sections from
testis cDNA and genomic DNA, and the N-terminal portion of the coding sequence
was assembled in pBS-KS using a three-part ligation and an internal
DraIII site. The entire coding sequence was then inserted into the
KpnI/NotI sites of pMT-HA
(Bunch et al., 1988) by means
of another three-part ligation, this time using an internal BamHI
site. The eIF4G protein coding sequence was amplified from testis
cDNA, cloned into pCRII-TOPO and inserted into the KpnI/SacI
sites of pMT-HA (Bunch et al.,
1988). The coding sequence of eIF4E1 was likewise
amplified from testes cDNA, ligated into pCRII-TOPO and inserted into the
SalI/SacI sites of pMT-Myc
(Bunch et al., 1988). The
eIF4E1 protein is one of the two polypeptides that are generated from the
eIF-4E (FlyBase) locus; eIF-4E-RA and eIF-4E-RC
encode eIF4E1 and eIF4E2, respectively
(Hernandez et al., 2005).
Tissue culture and co-immunoprecipitations
S2 cells were grown in Schneider's S2 cell media (Gibco) supplemented with
12.5% fetal bovine calf serum and 0.1 mg/ml gentamycin. Transfections were
performed (on cells split the same day) in six-well plates, using the
FuGENE-HD transfection reagent (Roche) and leaving the cells in the
transfection mix for 48 hours. All 2 ml of cells from each well was then
transferred to a T-75 flask, to which 13 ml of fresh media was added. Copper
sulfate was immediately added to a final concentration of 0.7 mM, and
induction proceeded for 24 hours. One-tenth volume was saved for crude extract
(+ 30 µl 2x protein loading buffer, boiled 5 minutes, frozen). The
remainder was pelleted, washed once with phosphate-buffered saline (PBS) and
resuspended in 500 µl cold lysis buffer [100 mM NaCl, 50 mM Tris, 2 mM
EDTA, 2 mM EGTA, 1% NP-40 + protease inhibitor tablet (Roche)] in a 1.5 ml
tube. The lysate was rocked for 20 minutes at 4°C and spun at full speed
in a microcentrifuge for 5 minutes. The supernatant was transferred to a fresh
tube, to which 20 µl anti-HA beads (3F10, Roche) was added. The anti-HA
immunoprecipitation (IP) samples were incubated for 3 hours at 4°C, washed
3x with cold lysis buffer and 1x with cold PBS. 25 µl 2x
loading buffer was added to the beads, and the samples were boiled for 5
minutes. Samples were run on a 4-20% gradient minigel (BioRad). Proteins were
subsequently transferred to a BioRad Immunoblot PVDF membrane overnight at
25-30 V. The blot was then blocked in 5% milk in Tris-buffered saline (TBS)
for 2 hours, incubated with primary antibody (anti-HA or anti-Myc, 1:5000)
(16B12, Covance and 4A6, Upstate) for 1 hour (5% milk/TBS), and secondary
antibody (HRP-anti-mouse, 1:5000; Jackson ImmunoResearch) for 1 hour, then
washed in several changes of TBS over 1.5 hours. Detection was performed using
Western Lightning ECL detection reagents (Amersham Biosciences).
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RESULTS |
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TOPSUMMARYINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). The
predicted protein encoded by CG10192 (eIF4G2) contained the
conserved, signature middle domain [39% identical to the middle domain of
human eIF4GI (EIF4G1-HUGO), 42% identical to the fly eIF4G], which is known in
human eIF4GI to bind eIF4A and eIF3
(Imataka and Sonenberg, 1997).
The predicted eIF4G2 protein also contained a region resembling the
alpha-helical MA3 domain found in other eIF4Gs and their homologs
(Fig. 1A). However, the
predicted eIF4G2 protein lacked the eIF5C domain [a domain of unknown function
found in the C termini of eIF4Gs and some other translation factors
(Marchler-Bauer et al., 2007)]
and had a long N-terminal region (1124 amino acids, compared with 418 for
eIF4G and 752 for human eIF4GI) with no homology to any known protein domains.
The predicted eIF4G2 protein lacked a canonical eIF4E-binding site
[YXXXXL
, where is a hydrophobic residue
(Mader et al., 1995)] at the
stereotypical distance from the middle domain (roughly 100-150 residues
N-terminal). However, epitope-tagged eIF4E1 co-immunoprecipitated with eIF4G2
when both were expressed in Drosophila tissue culture cells,
indicating that eIF4G2 directly or indirectly associates with the cap-binding
protein eIF4E1. Either HA-tagged eIF4G2 or HA-tagged canonical eIF4G was
co-expressed in S2 cells with Myc-tagged eIF4E1. Immunoprecipitation of
HA-eIF4G via the HA epitope tag resulted in co-immunoprecipitation of
Myc-eIF4E1, as expected, visualized by western blot of the precipitate with
anti-Myc (Fig. 1B, lane 2).
Likewise, even though the HA-eIF4G2 was either less abundantly expressed or
transferred to the blot less efficiently than HA-eIF4G
(Fig. 1B, lane 6), when eIF4G2
was immunoprecipitated via the HA tag, Myc-eIF4E1 co-immunoprecipitated
(Fig. 1B, lane 3). The
co-immunoprecipitation of Myc-eIF4E1 with HA-eIF4G2 supports the idea, based
on the conservation of the key middle domain, that eIF4G2 may also act in
translation initiation. Consistent with this, eIF4G2 was shown in the
accompanying paper to associate with 7-methyl-GTP-sepharose, a cap analog
(Franklin-Dumont et al.,
2007).
eIF4G2 is required for male fertility
Several strong loss-of-function alleles of eIF4G2 were recovered
in a variety of screens for mutants that affect male fertility (see Materials
and methods). Trans-heteroallelic combinations of these alleles resulted in
testes that contained plentiful spermatocytes but completely lacked elongated
spermatids or mature sperm (Fig.
2C,D). Recombination mapping and deficiency complementation
localized a representative allele to the region defined by deficiency
Df(3R)mbc1, which failed to complement the male sterile phenotype.
Sequence analysis of eIF4G2, which lies in this interval, revealed
mutations in the eIF4G2 coding region for each of the four alleles
tested. Two alleles had early stop codons and one a splice site mutation, all
three resulting in partial or complete deletion of the signature conserved
middle domain of the protein and therefore likely to be strong
loss-of-function mutations (Fig.
2A). The fourth allele had a missense mutation in the conserved
middle domain that changed a methionine to lysine in a position where the
residue is invariably hydrophobic across species. The equivalent residue in
human eIF4GII occurs in helix 5b
(Marcotrigiano et al., 2001).
Two nearby residues in the equivalent helix of human eIF4GI are required
together for binding of both eIF4A and eIF3
(Imataka and Sonenberg,
1997).
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eIF4G2 is expressed in a stage-specific pattern in the testis
In situ hybridization to testes revealed that eIF4G2 mRNA was
strongly expressed in differentiating male germ cells from early spermatocytes
to elongating spermatids (Fig.
3A). By contrast, eIF4G mRNA was present at the apical
tip of the testis, in mitotic cells and early spermatocytes
(Fig. 3C). The domains in which
eIF4G and eIF4G2 transcripts were detected overlapped in
early spermatocytes. Consistent with the distribution of eIF4G2 mRNA,
epitope-tagged eIF4G2 protein expressed from the rescuing genomic transgene
was detected in male germ cells starting from the early spermatocyte stage to
elongating spermatids (Fig.
3E,F).
The eIF4G2 transcript was detected by RT-PCR in females and agametic males (data not shown). Flies mutant for the strong loss-of-function alleles of eIF4G2 were viable and female fertile, however, suggesting that function of eIF4G2 is required mainly for spermatogenesis.
eIF4G2 is required in males for meiotic division
Testes from eIF4G2 mutant males had early germ cells, including
spermatogonia and spermatocytes (Fig.
4C,D). However, spermatocytes did not appear to properly execute
the meiotic divisions. In wild type, entry into meiotic division is
accompanied by condensation of the chromosomes, which subsequently move to the
metaphase plate at the center of the nucleus
(Fig. 4F;
Fig. 4J, arrow), then separate
in anaphase (Fig. 4J,
arrowheads). Spermatocytes in eIF4G2 mutant males were formed, and
meiotic chromosomes initiated condensation in preparation for the G2/M
transition of meiosis I (Fig.
4H). However, meiotic chromosomes neither condensed completely nor
moved to the center of the nucleus in eIF4G2 mutant spermatocytes,
and no metaphase or anaphase figures were detected, indicating that
spermatocytes in eIF4G2 males fail to undergo the major events of
meiotic division.
Translation of two key meiotic cell cycle regulatory proteins requires eIF4G2
Function of eIF4G2 was required for the dramatic upregulation of the key
cell cycle regulatory proteins Twine and CycB that normally takes place in
mature spermatocytes. In wild type, the level of CycB protein is low in
immature primary spermatocytes, rising in mature spermatocytes just before
onset of the G2/M transition for meiosis I. CycB protein is then abruptly
degraded at the metaphase to anaphase transition of meiosis I
(White-Cooper et al., 1998)
(Fig. 5A). The increase in
expression of CycB protein was not detected in spermatocytes mutant for
eIF4G2 (Fig. 5B), even
though, based on chromatin condensation state
(Fig. 4H), eIF4G2
mutant spermatocytes reached a stage in meiotic progression in which the
increase of CycB levels would normally take place
(White-Cooper et al., 1998).
The meiotic Cdc25 phosphatase Twine triggers the G2/M transition of meiosis I.
In wild-type mature spermatocytes, translation of twine in
preparation for entry into the meiotic divisions
(Alphey et al., 1992) can be
visualized by expression of ß-galactosidase from a twine-lacZ
reporter transgene. For testes from males heterozygous for eIF4G2 and
carrying one copy of the twine-lacZ reporter, each of the eight
testes examined had cysts positive for ß-galactosidase staining
(Fig. 5C). In eIF4G2
mutant spermatocytes, however, we did not detect expression of
ß-galactosidase from the twine-lacZ reporter in any of the 12
testes examined (Fig. 5D),
suggesting that expression of the twine reporter is much reduced in
spermatocytes lacking eIF4G2 function. Both cycB and twine
transcripts were expressed in eIF4G2 mutant spermatocytes, as in wild
type (Fig. 5F,H), indicating
that eIF4G2 is required for translation, not transcription or mRNA stability,
of cycB and twine in spermatocytes. Lack of the normal
increased expression levels of Twine and CycB proteins in eIF4G2
mutant spermatocytes was not likely to be because of arrest of
spermatogenesis, as male germ cells proceeded to early spermatid stages in the
mutant (Fig. 6).
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). This is consistent with the model that the failure
to execute major events of meiosis observed in eIF4G2 mutant male
germ cells may in part reflect lack of key cell cycle regulators for the G2/M
transition of meiosis I. A fraction of late-stage eIF4G2 mutant germ cells appeared to initiate spermatid elongation (Fig. 6G,H). To examine the extent to which eIF4G2 mutant germ cells are capable of differentiating, we examined the morphology of late-stage and terminal germ cells stained with anti-tubulin, as well as the expression of two spermatid differentiation markers, Fzo and Dj, by immunofluorescence microscopy. In wild-type elongating spermatids, microtubules aligned along the length of the cell are easily visible by anti-tubulin immunofluorescence (Fig. 7B, arrowheads). In terminal-stage eIF4G2 mutant germ cells, arrays of parallel microtubules were detected in the cells that had initiated (defective) elongation (Fig. 7D, arrowheads).
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). Fzo
protein localizes to the mitochondrial derivative in wild-type spermatids
(Fig. 7F, arrowheads). In the
eIF4G2 mutant, Fzo protein was detected in late-stage germ cells in a
cloud next to the nucleus (Fig.
7H, arrowheads), resembling the unfused mitochondrial aggregates
observed by phase-contrast microscopy in mutant spermatids. Likewise, although
expression of dj mRNA initiates in early spermatocytes, translation
of dj is normally delayed until well after completion of the meiotic
divisions (Santel et al.,
1997). The Dj-green fluorescent protein (GFP) fusion protein marks
elongated spermatids in wild type (Fig.
7I), localizing to the mitochondrial derivative within each
flagellum (Santel et al.,
1998; Santel et al.,
1997). In eIF4G2 mutant testes, Dj-GFP colocalized with
the aggregated mitochondria in late-stage cells
(Fig. 7J, arrowheads). |
DISCUSSION |
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TOPSUMMARYINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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;
Cho et al., 2006;
Cho et al., 2005;
Dinkova et al., 2005;
Hernandez et al., 2005;
Joshi et al., 2004;
Robalino et al., 2004), less
is known about the potential for the core eIF4G subunit to show such tissue
specificity. In a human hematopoetic stem cell line, eIF4GII is specifically
recruited to 5' cap structures of mRNAs upon thrombopoietin-mediated
induction of megakaryocyte differentiation, whereas levels of eIF4GI at the
cap remain constant (Caron et al.,
2004). However, the authors acknowledge that this recruitment of
eIF4GII could represent an overall increase in active initiation factor
complex within differentiating megakaryocytes, rather than intrinsic
transcript specificity on the part of eIF4GII.
|
;
Hiller et al., 2001;
Lin et al., 1996). By
contrast, in eIF4G2 mutant males, germ cells appear to skip the major
events of meiotic division but initiate spermatid differentiation. Germ cells
in males mutant for the cell cycle phosphatase Twine, or
cdc2ts mutant males shifted to the non-permissive
temperature, also skip the major events of meiotic division but proceed to
execute spermatid differentiation (Alphey
et al., 1992; Sigrist et al.,
1995). These data show that initiation and execution of the
spermatid differentiation program can proceed even when male germ cells fail
to execute the meiotic divisions. The failure to undergo the meiotic divisions in eIF4G2 is likely to be due, at least in part, to failure to upregulate twine and cycB translation as spermatocytes mature. Although eIF4G2 is a homolog of a known translation initiation factor, and eIF4G2 mutant spermatocytes have defects in translation of cycB and twine, it is formally possible that eIF4G2 does not act directly on these transcripts, but rather on an upstream regulator of their translation. Future experiments will address whether eIF4G2 binds these two mRNAs, to determine whether its effect on their translation is likely to be direct or indirect.
Function of eIF4G2 also appears to be required for many aspects of
spermatid differentiation. Although early spermatids form in eIF4G2
mutant males, the mitochondrial cloud fails to condense and form a compact
mitochondrial derivative, and very little spermatid elongation takes place.
The defects in spermatid differentiation in eIF4G2 mutant males are
more severe than the defects observed in males mutant for the RNA-binding
protein Boule, homolog of human BOULE and DAZL
(Eberhart et al., 1996). These
observations suggest that although both Boule and eIF4G2 are required for
normal translation of twine
(Maines and Wasserman, 1999),
the requirement for eIF4G2 is more widespread. A broad requirement for eIF4G2
for timing or execution of many events during male germ cell differentiation
is reflected in the pleiotropic nature of the eIF4G2 mutant phenotype
in testes. As shown in the accompanying paper
(Franklin-Dumont et al.,
2007), loss-of-function of eIF4G2 also affects spermatocyte growth
as well as timing of events of the meiotic program in primary
spermatocytes.
Given the broad defects observed in male germ cells, the predicted role of eIF4G2 in translation initiation, and the apparent reduction in transcript levels for the canonical eIF4G, it was surprising that Fzo and Dj proteins were expressed in spermatids from eIF4G2 mutant males. These findings suggest that eIF4G2 is not required (directly or indirectly) for translation of all mRNAs in mature spermatocytes and post-meiotic germ cells. It is possible that some of the canonical eIF4G protein persists from earlier germ cell stages, sufficient for translation of fzo and dj. However, if so, this is not sufficient for robust translation of cell cycle regulators twine and cycB in late spermatocytes, or for sufficient translation of additional mRNAs required for proper spermatid differentiation.
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ACKNOWLEDGMENTS |
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REFERENCES |
|---|
|
TOPSUMMARYINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Alphey, L., Jimenez, J., White-Cooper, H., Dawson, I., Nurse, P. and Glover, D. M. (1992). Twine, a CDC25 homolog that functions in the male and female germline of Drosophila. Cell 69,977 -988.[CrossRef][Medline]
Amiri, A., Keiper, B. D., Kawasaki, I., Fan, Y., Kohara, Y. and Rhoads, R. E. (2001). An isoform of eIF4E is a component of germ granules and is required for spermatogenesis in C. elegans. Development 128,3899 -3912.[Medline]
Bunch, T. A., Grinblat, Y. and Goldstein, L. S.
(1988). Characterization and use of the Drosophila
metallothionein promoter in cultured Drosophila melanogaster cells.
Nucleic Acids Res. 16,1043
-1061.
Caron, S., Charon, M., Cramer, E., Sonenberg, N. and
Dusanter-Fourt, I. (2004). Selective modification of
eukaryotic initiation factor 4F (eIF4F) at the onset of cell differentiation:
recruitment of eIF4GII and long-lasting phosphorylation of eIF4E.
Mol. Cell. Biol. 24,4920
-4928.
Chen, X. and Fischer, J. A. (2002). A P element transformation vector for high levels of gene expression in germ-line cells of the ovary and undifferentiated cells in the developing eye of Drosophila. Plasmid 47,61 -65.[CrossRef][Medline]
Cho, P. F., Poulin, F., Cho-Park, Y. A., Cho-Park, I. B., Chicoine, J. D., Lasko, P. and Sonenberg, N. (2005). A new paradigm for translational control: inhibition via 5'-3' mRNA tethering by Bicoid and the eIF4E cognate 4EHP. Cell 121,411 -423.[CrossRef][Medline]
Cho, P. F., Gamberi, C., Cho-Park, Y. A., Cho-Park, I. B., Lasko, P. and Sonenberg, N. (2006). Cap-dependent translational inhibition establishes two opposing morphogen gradients in Drosophila embryos. Curr. Biol. 16,2035 -2041.[CrossRef][Medline]
Dinkova, T. D., Keiper, B. D., Korneeva, N. L., Aamodt, E. J.
and Rhoads, R. E. (2005). Translation of a small subset of
Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic
translation initiation factor 4E isoform. Mol. Cell.
Biol. 25,100
-113.
Eberhart, C. G., Maines, J. Z. and Wasserman, S. A. (1996). Meiotic cell cycle requirement for a fly homologue of human Deleted in Azoospermia. Nature 381,783 -785.[CrossRef][Medline]
Franklin-Dumont, T. M., Chatterjee, C., Wasserman, S. A. and
DiNardo, S. (2007). A novel eIF4G homolog, Off-schedule,
couples translational control to meiosis and differentiation in
Drosophila spermatocytes. Development
134,2851
-2861.
Fuller, M. T. (1986). Genetic analysis of spermatogenesis in Drosophila: the role of the testis-specific beta-tubulin and interacting genes in cellular morphogenesis. In Gametogenesis and the Early Embryo (ed. J. G. Gall), pp. 19-41. New York: Alan Liss.
Giorgini, F., Davies, H. G. and Braun, R. E.
(2002). Translational repression by MSY4 inhibits spermatid
differentiation in mice. Development
129,3669
-3679.
Glover, D. M. and Gonzalez, C. (1993). Techniques for studying mitosis in Drosophila. In The Cell Cycle: A Practical Approach (ed. R. Brookes and P. Fantes), pp.163 -168.Oxford: IRL Press.
Groisman, I., Huang, Y. S., Mendez, R., Cao, Q. and Richter, J. D. (2001). Translational control of embryonic cell division by CPEB and maskin. Cold Spring Harb. Symp. Quant. Biol. 66,345 -351.[CrossRef][Medline]
Hales, K. G. and Fuller, M. T. (1997). Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 90,121 -129.[CrossRef][Medline]
Hempel, L. U., Rathke, C., Raja, S. J. and Renkawitz-Pohl, R. (2006). In Drosophila, don juan and don juan like encode proteins of the spermatid nucleus and the flagellum and both are regulated at the transcriptional level by the TAF II80 cannonball while translational repression is achieved by distinct elements. Dev. Dyn. 235,1053 -1064.[CrossRef][Medline]
Hernandez, G., Altmann, M., Sierra, J. M., Urlaub, H., Diez del Corral, R., Schwartz, P. and Rivera-Pomar, R. (2005). Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila. Mech. Dev. 122,529 -543.[CrossRef][Medline]
Hiller, M. A., Lin, T. Y., Wood, C. and Fuller, M. T.
(2001). Developmental regulation of transcription by a
tissue-specific TAF homolog. Genes Dev.
15,1021
-1030.
Hiller, M., Chen, X., Pringle, M. J., Suchorolski, M., Sancak,
Y., Viswanathan, S., Bolival, B., Lin, T. Y., Marino, S. and Fuller, M. T.
(2004). Testis-specific TAF homologs collaborate to control a
tissue-specific transcription program. Development
131,5297
-5308.
Hime, G. R., Brill, J. A. and Fuller, M. T. (1996). Assembly of ring canals in the male germ line from structural components of the contractile ring. J. Cell Sci. 109,2779 -2788.[Abstract]
Imataka, H. and Sonenberg, N. (1997). Human eukaryotic translation initiation factor 4G (eIF4G) possesses two separate and independent binding sites for eIF4A. Mol. Cell. Biol. 17,6940 -6947.[Abstract]
Joshi, B., Cameron, A. and Jagus, R. (2004). Characterization of mammalian eIF4E-family members. Eur. J. Biochem. 271,2189 -2203.[Medline]
Kuersten, S. and Goodwin, E. B. (2003). The power of the 3' UTR: translational control and development. Nat. Rev. Genet. 4,626 -637.[CrossRef][Medline]
Lin, T. Y., Viswanathan, S., Wood, C., Wilson, P. G., Wolf, N. and Fuller, M. T. (1996). Coordinate developmental control of the meiotic cell cycle and spermatid differentiation in Drosophila males. Development 122,1331 -1341.[Abstract]
Mader, S., Lee, H., Pause, A. and Sonenberg, N. (1995). The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins. Mol. Cell. Biol. 15,4990 -4997.[Abstract]
Maines, J. Z. and Wasserman, S. A. (1999). Post-transcriptional regulation of the meiotic Cdc25 protein Twine by the Dazl orthologue Boule. Nat. Cell Biol. 1, 171-174.[CrossRef][Medline]
Marchler-Bauer, A., Anderson, J. B., Derbyshire, M. K., DeWeese-Scott, C., Gonzales, N. R., Gwadz, M., Hao, L., He, S., Hurwitz, D. I., Jackson, J. D. et al. (2007). CDD: a conserved domain database for interactive domain family analysis. Nucleic Acids Res. 35,D237 -D240.[CrossRef][Medline]
Marcotrigiano, J., Lomakin, I. B., Sonenberg, N., Pestova, T. V., Hellen, C. U. and Burley, S. K. (2001). A conserved HEAT domain within eIF4G directs assembly of the translation initiation machinery. Mol. Cell 7,193 -203.[CrossRef][Medline]
Robalino, J., Bhavesh, J., Fahrenkrug, S. C. and Jagus, R.
(2004). Two zebrafish eIF4E family members are differentially
expressed and functionally divergent. J. Biol. Chem.
279,10532
-10541.
Rubin, G. M. and Spradling, A. C. (1982).
Genetic transformation of Drosophila with transposable element vectors.
Science 218,348
-353.
Santel, A., Winhauer, T., Blumer, N. and Renkawitz-Pohl, R. (1997). The Drosophila don juan (dj) gene encodes a novel sperm specific protein component characterized by an unusual domain of a repetitive amino acid motif. Mech. Dev. 64, 19-30.[CrossRef][Medline]
Santel, A., Blumer, N., Kampfer, M. and Renkawitz-Pohl, R. (1998). Flagellar mitochondrial association of the male-specific Don Juan protein in Drosophila spermatozoa. J. Cell Sci. 111,3299 -3309.[Abstract]
Schafer, M., Kuhn, R., Bosse, F. and Schafer, U. (1990). A conserved element in the leader mediates post-meiotic translation as well as cytoplasmic polyadenylation of a Drosophila spermatocyte mRNA. EMBO J. 9,4519 -4525.[Medline]
Sigrist, S., Ried, G. and Lehner, C. F. (1995). Dmcdc2 kinase is required for both meiotic divisions during Drosophila spermatogenesis and is activated by the Twine/cdc25 phosphatase. Mech. Dev. 53,247 -260.[CrossRef][Medline]
Tarun, S. Z., Jr and Sachs, A. B. (1996). Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G. EMBO J. 15,7168 -7177.[Medline]
Vasudevan, S., Seli, E. and Steitz, J. A.
(2006). Metazoan oocyte and early embryo development program: a
progression through translation regulatory cascades. Genes
Dev. 20,138
-146.
Wakimoto, B. T., Lindsley, D. L. and Herrera, C.
(2004). Toward a comprehensive genetic analysis of male fertility
in Drosophila melanogaster. Genetics
167,207
-216.
White-Cooper, H., Schafer, M. A., Alphey, L. S. and Fuller, M. T. (1998). Transcriptional and post-transcriptional control mechanisms coordinate the onset of spermatid differentiation with meiosis I in Drosophila. Development 125,125 -134.[Abstract]
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