RRC ID 75981
Author Jeyasimman D, Ercan B, Dharmawan D, Naito T, Sun J, Saheki Y.
Title PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans.
Journal Nat Commun
Abstract Different types of cellular membranes have unique lipid compositions that are important for their functional identity. PI(4,5)P2 is enriched in the plasma membrane where it contributes to local activation of key cellular events, including actomyosin contraction and cytokinesis. However, how cells prevent PI(4,5)P2 from accumulating in intracellular membrane compartments, despite constant intermixing and exchange of lipid membranes, is poorly understood. Using the C. elegans early embryo as our model system, we show that the evolutionarily conserved lipid transfer proteins, PDZD-8 and TEX-2, act together with the PI(4,5)P2 phosphatases, OCRL-1 and UNC-26/synaptojanin, to prevent the build-up of PI(4,5)P2 on endosomal membranes. In the absence of these four proteins, large amounts of PI(4,5)P2 accumulate on endosomes, leading to embryonic lethality due to ectopic recruitment of proteins involved in actomyosin contractility. PDZD-8 localizes to the endoplasmic reticulum and regulates endosomal PI(4,5)P2 levels via its lipid harboring SMP domain. Accumulation of PI(4,5)P2 on endosomes is accompanied by impairment of their degradative capacity. Thus, cells use multiple redundant systems to maintain endosomal PI(4,5)P2 homeostasis.
Volume 12(1)
Pages 6065
Published 2021-10-18
DOI 10.1038/s41467-021-26177-z
PII 10.1038/s41467-021-26177-z
PMID 34663803
PMC PMC8523718
MeSH Actomyosin / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Membrane / metabolism Cytokinesis Embryonic Development Endocytosis / physiology* Endoplasmic Reticulum / metabolism Endosomes / metabolism* Homeostasis Membrane Proteins / genetics Membrane Proteins / metabolism* Nerve Tissue Proteins Phosphatidylinositols Phosphoric Monoester Hydrolases
Resource
C.elegans tm10626