Genetics, Vol. 179, 375-387, May 2008, Copyright © 2008
doi:10.1534/genetics.108.087247

Caenorhabditis elegans num-1 Negatively Regulates Endocytic Recycling

Lars Nilsson*, Barbara Conradt{dagger}, Anne-Françoise Ruaud{ddagger}, Carlos Chih-Hsiung Chen§, Julia Hatzold{dagger}, Jean-Louis Bessereau{ddagger}, Barth D. Grant§ and Simon Tuck*,1

* Umeå Center for Molecular Pathogenesis, Umeå University, SE-901 87 Umeå, Sweden, {dagger} Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755-3837, {ddagger} ENS, Biologie Cellulaire de la Synapse, F-75005 Paris, France and Inserm, U789, F-75005 Paris, France and § Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854

1 Corresponding author: UCMP Molecular Medicine Bldg., 6M Room 6018, Analysvägen 1, Umeå University, SE-901 87 Umeå, Sweden.
E-mail: simon.tuck{at}ucmp.umu.se

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 Caenorhabditis elegans endocytic recycling is inhibited by NUM-1A, the nematode Numb homolog. 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 in both 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.


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Genetics 2008 179: NP. [Full Text]