The trafficking of vesicles/membrane between different
compartments of a cell is an essential process in all eukaryotic cells
and is used to maintain cellular integrity, to interact with the extracellular
environment, and to generally modulate various cellular activities.
Numerous advances have been made in understanding different pathways
of vesicle trafficking and in elucidating some of the factors that
regulate them; these advances have demonstrated a striking conservation
of these pathways among all eukaryotic cells.
We have taken a genetic approach to study vesicle trafficking
in the nematode C. elegans whose small size, ease of handling,
and sequenced genome makes it perfectly suited for that purpose. We
have concentrated on two separate pathways: 1) endocytosis of extracellular
material by scavenger cells, and 2) polarized secretion by an epithelial
cell sheet.
There are six cells called coelomocytes in the body
cavity of C. elegans that constitutively endocytose fluid.
We have established as assay whereupon GFP secreted into the body
cavity is taken up by these cells and have identified several genes
involved in this process. Future plans include studying the function
of these genes in this process and identifying other genes using forward
and reverse genetic approaches. The comparative analysis of endocytosis
in C. elegans and in other systems should give us a better
understanding of this central biological process.
The C. elegans hypodermis is a polarized epithelial
layer with well defined apical and basolateral domains. We have shown
that GFP secreted from these cells is targeted to the apical domain.
We have used this assay to screen for mutants defective in this process
and have identified some genes involved in this process. Future plans
include the analysis of these genes and the identification of others
that function in regulating the targeted delivery of vesicles. The
aim is to better understand how epithelial cells establish and maintain
their polarity.
Any link on the below references will take you off
of the BMCB site and to an abstract of that particular paper.
Schaheen, L., G. Patton, and H. Fares. 2006. Suppression
of the cup-5 Mucolipidosis Type IV-related lysosomal dysfunction by
the inactivation of an ABC Transporter in C. elegans. Development (in press).
Nicot, A.-S., H. Fares, B. Payrastre, A. Chisholm, M.
Labouesse, and H. Laporte. 2006. The phosphoinositide kinase PIKfyve/Fab1p
regulates terminal lysosome maturation in Caenorhabditis elegans. Molecular Biology of the Cell 7: 3062-3074.
Schaheen, L., H. Dang, and H. Fares. 2006. Basis of
lethality in C. elegans lacking CUP-5, the Mucolipidosis Type
IV orthologue. Developmental
Biology 293: 382-391.
Patton, A., S. Knuth, B. Schaheen, H. Dang, I. Greenwald,
and H. Fares. 2005. Endocytosis function of a ligand-gated ion channel
homolog in Caenorhabditis elegans. Current
Biology 15: 1045-1050.
Treusch, S., W. Knuth, S.A. Slaugenhaupt, E. Goldin,
B.D. Grant, and H. Fares. 2004. Caenorhabiditis elegans functional
orthologue/human protein h-mucolipin-1 is required for lysosome biogenesis. Proceedings of the National Academy of Sciences U.S.A. 101: 4483-4488.
Dang, H., Z. Li, E.Y. Skolnik, and H. Fares. 2004. Disease-related
myotubularins function in endocytic traffic. Molecular
Biology of the Cell 15: 189-196.
Xue, Y., H. Fares, B. Grant, Z. Li, S.G. Clark, and
E.Y. Skolnik. 2003. Genetic analysis of the myotubularin family of
phosphatases in Caenorhabditis elegans. Journal
of Biological Chemistry 278: 34380-34386.
Fares, H., and I. Greenwald. 2001. Regulation of endocytosis
by CUP-5, the Caenorhabditis elegans mucolipin-1 homologue.
Nature Genetics 28: 64-68.
Fares, H., and I. Greenwald. 2001. Genetic analysis
of endocytosis in Caenorhabditis elegan: coelomocyte uptake
defective mutants. Genetics 159: 133-145.
Fares, H., and B. Grant. 2002. Deciphering endocytosis
in Caenorhabditis elegans. Traffic 3:11-19.
