Caenorhabditis elegans num-1 negatively regulates endocytic recycling

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)