RRC ID 46480
Author Zhang H, Kim A, Abraham N, Khan LA, Hall DH, Fleming JT, Gobel V.
Title Clathrin and AP-1 regulate apical polarity and lumen formation during C. elegans tubulogenesis.
Journal Development
Abstract Clathrin coats vesicles in all eukaryotic cells and has a well-defined role in endocytosis, moving molecules away from the plasma membrane. Its function on routes towards the plasma membrane was only recently appreciated and is thought to be limited to basolateral transport. Here, an unbiased RNAi-based tubulogenesis screen identifies a role of clathrin (CHC-1) and its AP-1 adaptor in apical polarity during de novo lumenal membrane biogenesis in the C. elegans intestine. We show that CHC-1/AP-1-mediated polarized transport intersects with a sphingolipid-dependent apical sorting process. Depleting each presumed trafficking component mislocalizes the same set of apical membrane molecules basolaterally, including the polarity regulator PAR-6, and generates ectopic lateral lumens. GFP::CHC-1 and BODIPY-ceramide vesicles associate perinuclearly and assemble asymmetrically at polarized plasma membrane domains in a co-dependent and AP-1-dependent manner. Based on these findings, we propose a trafficking pathway for apical membrane polarity and lumen morphogenesis that implies: (1) a clathrin/AP-1 function on an apically directed transport route; and (2) the convergence of this route with a sphingolipid-dependent apical trafficking path.
Volume 139(11)
Pages 2071-83
Published 2012-6-1
DOI 10.1242/dev.077347
PII dev.077347
PMID 22535410
PMC PMC3347694
MeSH Adaptor Protein Complex 1 / metabolism Adaptor Protein Complex 1 / physiology* Animals Caenorhabditis elegans / embryology* Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Cell Polarity / physiology* Clathrin Heavy Chains / metabolism Clathrin Heavy Chains / physiology* Green Fluorescent Proteins Intestines / cytology Intestines / embryology* Microscopy, Electron, Transmission Microscopy, Fluorescence Protein Transport / physiology RNA Interference Sphingosine / analogs & derivatives Transport Vesicles / metabolism
IF 5.763
Times Cited 33
C.elegans tm2866 tm935 tm1369 tm1425