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Fig. 1. Relevant background information. (A) In the third larval stage, an
inductive signal (black arrow) from the gonadal anchor cell (AC) and a lateral
signal (gray arrows) from P6.p impose a
3°-3°-2°-1°-2°-3° pattern of cell fates on six
equivalent VPCs, P3.p-P8.p. Cell fates can be distinguished by appropriate
markers (see text and legends of Figs
5,
6). (B) Full-length LIN-12,
with hallmark regions of EGF-like (EGF), LIN-12/Notch repeat (LNR),
cdc10/ankyrin (ANK) repeat and PEST sequence (P). The position of the green
fluorescent protein (GFP) tag is also shown. `Region 1' (r1) was shown to be
sufficient to promote downregulation of membrane tethered GFP in P6.p
(Shaye and Greenwald, 2002).
(C) Canonical endocytic downregulation. Sub-apical adherens junctions (AJ),
marked by the protein AJM-1 (Koppen et
al., 2001), separate the apical surface from the basolateral
surface. A receptor (white bar: extracellular domain; hatched bar:
intracellular domain) marked for downregulation is internalized and trafficked
to early endosomes (EE). From EEs, receptors that are tagged for
downregulation are trafficked to late endosomes (LE)/multi-vesicular endosomes
(MVE). An MVE-sorting step, by which the receptor is sorted into invaginating
lumenal vesicles, removes the intracellular domain from the cytosol. MVE
lumenal vesicles are delivered to the lysosome. (D) The first 45 amino acids
of region 1 from LIN-12 and GLP-1 in C. elegans (Ce), C. briggsae
(Cb) and C. remanei (Cr)
(Rudel and Kimble, 2001;
Rudel and Kimble, 2002) have
regions of conservation. The DTS is boxed, and conserved residues analyzed in
this study are marked by asterisks. The conserved CSL-binding region
(Kovall and Hendrickson, 2004)
is also indicated. Alignments were obtained with the ClustalW feature of
MacVector (Accelrys).
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