A C. elegans CLIC-like Protein Required for Intracellular Tube Formation and Maintenance

Abstract

The Caenorhabditis elegans excretory canal is composed of a single elongated and branched cell that is tunneled by an inner lumen of apical character. Loss of the exc-4 gene causes a cystic enlargement of this intracellular tube. exc-4 encodes a member of the chloride intracellular channel (CLIC) family of proteins. EXC-4 protein localizes to various tubular membranes in distinct cell types, including the lumenal membrane of the excretory tubes. A conserved 55-amino acid domain enables EXC-4 translocation from the cytosol to the lumenal membrane. The tubular architecture of this membrane requires EXC-4 for both its formation and maintenance.

Chloride Intracellular Channel Protein-4 Functions in Angiogenesis by Supporting Acidification of Vacuoles Along the Intracellular Tubulogenic Pathway

“…Each of the two CLICs encoded by C. elegans is able to support tubulogenesis and only cell-specific expression prevents functional complementation in vivo. 6,32 In mammals, CLIC1 is widely expressed in virtually all tissues and cell types and is present in primary cultures of mouse endothelial cells (not shown). Our hypothesis is that functional redundancy between CLIC4 and other CLICs is adequate to allow a fraction of Clic4 Ϫ/Ϫ mice to survive through embryogenesis to birth and to allow essentially normal postnatal growth and development in the unstressed laboratory environment.…”

“…4 CLICs are a family of proteins that have been implicated as intracellular chloride channels, but whose physiological roles remain uncertain. 5 A CLIC family member has been shown to be essential for the cellhollowing tubulogenesis of the excretory cell of Caenorhabditis elegans 6 in which it is necessary for intracellular vesicles to fuse into an intact intracellular tube although its specific role in this process is unknown. Furthermore, CLIC4 (one of six mammalian CLICs) has been implicated in endothelial cell tubulogenesis in a proteomics study.…”

Genes Required for Osmoregulation and Apical Secretion in Caenorhabditis elegans

“…The gene rdy-3 appears unique in our collection, since it was required for excretory canal formation but not for cuticle assembly. Future work should tell whether rdy-3 acts primarily to allow excretory lumen extension, as is the case for the chloride channel EXC-4 (Berry et al 2003), or if it also controls osmoregulation.…”

The specificity of interactions between proteins and sulfated polysaccharides

“…Expression of these isoforms, for example of HS6ST (heparan sulfate 6-O-sulfotransferase) and HS2ST (heparan sulfate 2-O-sulfotransferase), takes place in developing tissues in defi ned areas and at defi ned times ). This provides a mechanism by which specifi c affi nities of HS sequences for different growth factors and morphogens can form the gradients which give rise to correct formation of the developing embryo; for example in the nervous system (Bulow and Hobert 2004), heart (Yue et al 2004), limb buds (Berry et al 2003, Nogami et al 2004, and in cartilage (Kirn-Safran et al 2004). In the kidney, absence of 2-O-sulfation leads to failure of kidney development: 2-O-desulfation impairs binding of heparin to glial cell line-derived neurotrophic factor (Rickard et al 2003).…”