Clathrin and AP-1 regulate apical polarity and lumen formation during C. elegans tubulogenesis

Verena Gobel, Hongjie Zhang, Ahlee Kim, Nessy Abraham, Liakot A. Khan, David H. Hall, John T. Fleming

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2071-2083
Number of pages13
JournalDevelopment
Volume139
Issue number11
DOIs
StatePublished - Jun 1 2012

Keywords

  • AP-1
  • Caenorhabditis elegans
  • Clathrin
  • Polarity
  • Sphingolipids
  • Tubulogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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