TY - JOUR
T1 - WAVE/SCAR promotes endocytosis and early endosome morphology in polarized C. elegans epithelia
AU - Patel, Falshruti B.
AU - Soto, Martha
N1 - Funding Information:
We would like to thank the NCRR -funded Caenorhabditis Genetics Center, Hanna Fares, Todd Lamitina and Barth Grant, for strains, the NICHD -funded University of Iowa Hybridoma Bank for the antibodies to DYN-1, IFB-2 and ERM-1, Jon Audhya for antibodies to RAB-5, Renaud Legouis for the antibody to LET-413, Zhiyong Bai and Barth Grant for the RT2287 strain, and Barth Grant for antibodies to CHC-1, RME-2 and APA-2, and for advice on endocytosis assays and staining of adult intestines. Thanks to Dr. Carolina Wahlby at CellProfiler (Broad Institute) for advice on quantitation. We thank Barth Grant, Loren Runnels and two anonymous reviewers for helpful suggestions on the manuscript. This research was funded by grants from the NIH ( GM081670 ) and NSF ( 0641123 ) to M.C.S.
PY - 2013/5/15
Y1 - 2013/5/15
N2 - Cells can use the force of actin polymerization to drive intracellular transport, but the role of actin in endocytosis is not clear. Studies in single-celled yeast demonstrate the essential role of the branched actin nucleator, Arp2/3, and its activating nucleation promoting factors (NPFs) in the process of invagination from the cell surface through endocytosis. However, some mammalian studies have disputed the need for F-actin and Arp2/3 in Clathrin-Mediated Endocytosis (CME) in multicellular organisms. We investigate the role of Arp2/3 during endocytosis in Caenorhabditis elegans, a multicellular organism with polarized epithelia. Arp2/3 and its NPF, WAVE/SCAR, are essential for C. elegans embryonic morphogenesis. We show that WAVE/SCAR and Arp2/3 regulate endocytosis and early endosome morphology in diverse tissues of C. elegans. Depletion of WAVE/SCAR or Arp2/3, but not of the NPF Wasp, severely disrupts the distribution of molecules proposed to be internalized via CME, and alters the subcellular enrichment of the early endosome regulator RAB-5. Loss of WAVE/SCAR or of the GEFs that regulate RAB-5 results in similar defects in endocytosis in the intestine and coelomocyte cells. This study in a multicellular organism supports an essential role for branched actin regulators in endocytosis, and identifies WAVE/SCAR as a key NPF that promotes Arp2/3 endocytic function in C. elegans.
AB - Cells can use the force of actin polymerization to drive intracellular transport, but the role of actin in endocytosis is not clear. Studies in single-celled yeast demonstrate the essential role of the branched actin nucleator, Arp2/3, and its activating nucleation promoting factors (NPFs) in the process of invagination from the cell surface through endocytosis. However, some mammalian studies have disputed the need for F-actin and Arp2/3 in Clathrin-Mediated Endocytosis (CME) in multicellular organisms. We investigate the role of Arp2/3 during endocytosis in Caenorhabditis elegans, a multicellular organism with polarized epithelia. Arp2/3 and its NPF, WAVE/SCAR, are essential for C. elegans embryonic morphogenesis. We show that WAVE/SCAR and Arp2/3 regulate endocytosis and early endosome morphology in diverse tissues of C. elegans. Depletion of WAVE/SCAR or Arp2/3, but not of the NPF Wasp, severely disrupts the distribution of molecules proposed to be internalized via CME, and alters the subcellular enrichment of the early endosome regulator RAB-5. Loss of WAVE/SCAR or of the GEFs that regulate RAB-5 results in similar defects in endocytosis in the intestine and coelomocyte cells. This study in a multicellular organism supports an essential role for branched actin regulators in endocytosis, and identifies WAVE/SCAR as a key NPF that promotes Arp2/3 endocytic function in C. elegans.
KW - Actin nucleation
KW - Early endosomes
KW - Endocytosis
KW - Morphogenesis
KW - Nucleation promoting factors
UR - http://www.scopus.com/inward/record.url?scp=84876957706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876957706&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2013.03.012
DO - 10.1016/j.ydbio.2013.03.012
M3 - Article
C2 - 23510716
AN - SCOPUS:84876957706
VL - 377
SP - 319
EP - 332
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -