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Caenorhabditis elegans num-1 negatively regulates endocytic recycling
Umeå University, Faculty of Science and Technology, Umeå Centre for Molecular Pathogenesis (UCMP).
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2008 (English)In: Genetics, Vol. 179, 375-387 p.Article in journal (Refereed) Published
Abstract [en]

Much of the material taken into cells by endocytosis is rapidly returned to the plasma membrane by the endocytic recycling pathway. Although recycling is vital for the correct localization of cell membrane receptors and lipids, the molecular mechanisms that regulate recycling are only partially understood. Here we show that in C. elegans, endocytic recycling is inhibited by NUM-1A, the nematode Numb homologue. NUM-1A::GFP fusion protein is localized to the baso-lateral surfaces of many polarized epithelial cells including the hypodermis and the intestine. We show that increased NUM-1A levels cause morphological defects in these cells similar to those caused by loss-of-function mutations in rme-1, a positive regulator of recycling both in C. elegans and mammals. We describe the isolation of worms lacking num-1A activity and show that, consistent with a model in which NUM-1A negatively regulates recycling in the intestine, loss of num-1A function bypasses the requirement for RME-1. Genetic epistasis analysis with rab-10, which is required at an early part of the recycling pathway, suggests that loss of num-1A function does not affect the uptake of material by endocytosis but rather inhibits baso-lateral recycling downstream of rab-10.

Place, publisher, year, edition, pages
2008. Vol. 179, 375-387 p.
Keyword [en]
Animals, Bacterial Proteins/genetics/*metabolism, Biofilms, Caenorhabditis elegans/cytology/*microbiology/*physiology, Cell Communication, Cell Line; Tumor, Cholera Toxin/metabolism, Feeding Behavior, Fimbriae; Bacterial/metabolism, Humans, Interleukin-8/secretion, Intestines/cytology/microbiology, Peptide Hydrolases/genetics/*metabolism, Predatory Behavior, Repressor Proteins/genetics/metabolism, Survival Rate, Trans-Activators/genetics/metabolism, Transcription Factors/genetics/metabolism, Vibrio cholerae/*enzymology/genetics/*pathogenicity
URN: urn:nbn:se:umu:diva-11320DOI: doi:10.1534/genetics.108.087247PubMedID: 18493060OAI: diva2:150991
Available from: 2008-12-14 Created: 2008-12-14 Last updated: 2011-01-10Bibliographically approved

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Nilsson, LarsTuck, Simon
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Umeå Centre for Molecular Pathogenesis (UCMP)

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