First published online December 21, 2007
Development 135, 206e (2008)
© The Company of Biologists Limited
Vesicle trafficking: transported into development and disease
Several inherited human diseases [such as arthrogryposis-renal
dysfunction-cholestasis and Hermansky-Pudlak (HP) syndromes] are associated
with defective vesicle transport, which is an essential process for many
cellular events. Now, Neuhauss, Dahm and colleagues identify the zebrafish
mutant leberknödel (lbk) as a model for such disorders
(see p. 387). These
mutants, like individuals with HP syndrome and similar disorders, have
hypopigmented skin melanocytes and a hypopigmented retinal pigment epithelium
(RPE). The mutant fish also have visual and immunological defects and defects
in various internal organs. The researchers identify the mutation in
lbk as a loss-of-function mutation in the gene encoding Vam6p/Vps39p,
which is required for the trafficking of lysosomes and lysosome-related
vesicles, such as melanosomes. They also report that macrophages and cells in
the RPE, liver and intestines of lbk mutants contain increased
numbers of enlarged intracellular vesicles compared with wild-type cells.
Overall, these results highlight vam6 as a novel candidate disease
gene and reveal its requirement for normal development for future research to
explore.
Related articles in Development:
- The zebrafish mutant lbk/vam6 resembles human multisystemic disorders caused by aberrant trafficking of endosomal vesicles
- Helia B. Schonthaler, Valerie C. Fleisch, Oliver Biehlmaier, Yuri Makhankov, Oliver Rinner, Ronja Bahadori, Robert Geisler, Heinz Schwarz, Stephan C. F. Neuhauss, and Ralf Dahm
Development 2008 135: 387-399.
[Abstract]
[Full Text]
