RRC ID 76037
Author Pushpa K, Dagar S, Kumar H, Pathak D, Mylavarapu SVS.
Title The exocyst complex regulates C. elegans germline stem cell proliferation by controlling membrane Notch levels.
Journal Development
Abstract The conserved exocyst complex regulates plasma membrane-directed vesicle fusion in eukaryotes. However, its role in stem cell proliferation has not been reported. Germline stem cell (GSC) proliferation in the nematode Caenorhabditis elegans is regulated by conserved Notch signaling. Here, we reveal that the exocyst complex regulates C. elegans GSC proliferation by modulating Notch signaling cell autonomously. Notch membrane density is asymmetrically maintained on GSCs. Knockdown of exocyst complex subunits or of the exocyst-interacting GTPases Rab5 and Rab11 leads to Notch redistribution from the GSC-niche interface to the cytoplasm, suggesting defects in plasma membrane Notch deposition. The anterior polarity (aPar) protein Par6 is required for GSC proliferation, and for maintaining niche-facing membrane levels of Notch and the exocyst complex. The exocyst complex biochemically interacts with the aPar regulator Par5 (14-3-3ζ) and Notch in C. elegans and human cells. Exocyst components are required for Notch plasma membrane localization and signaling in mammalian cells. Our study uncovers a possibly conserved requirement of the exocyst complex in regulating GSC proliferation and in maintaining optimal membrane Notch levels.
Volume 148(15)
Published 2021-8-1
DOI 10.1242/dev.196345
PII 271155
PMID 34338279
MeSH 14-3-3 Proteins / metabolism Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Cell Communication / physiology Cell Membrane / metabolism* Cell Membrane / physiology Cell Proliferation / physiology* Cytoplasm / metabolism Cytoplasm / physiology Eukaryota / metabolism Eukaryota / physiology Germ Cells / metabolism* Germ Cells / physiology* Membrane Fusion / physiology Morphogenesis / physiology Signal Transduction / physiology Stem Cell Niche / physiology*
Resource
C.elegans tm4536