| 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 |
5.611
|
| Times Cited |
33
|
|
WOS Category
|
DEVELOPMENTAL BIOLOGY
|
| Resource |
| C.elegans |
tm2866
tm935
tm1369
tm1425 |
