RRC ID 45684
Author Bai Z, Grant BD.
Title A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling.
Journal Proc Natl Acad Sci U S A
Abstract Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1-positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42-associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.
Volume 112(12)
Pages E1443-52
Published 2015-3-24
DOI 10.1073/pnas.1418651112
PII 1418651112
PMID 25775511
PMC PMC4378436
MeSH Actins / metabolism Adaptor Proteins, Signal Transducing / metabolism Animals Animals, Genetically Modified Biological Transport Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Endocytosis* Endosomes / metabolism* Humans Image Processing, Computer-Assisted Membrane Lipids / metabolism Membrane Proteins / metabolism* Microscopy, Confocal Protein Kinase C / metabolism RNA Interference cdc42 GTP-Binding Protein / metabolism* trans-Golgi Network / metabolism
IF 9.412
Times Cited 22
C.elegans tm2056 tm1320 tm1595 tm1523