RRC ID 15286
著者 Wehman AM, Poggioli C, Schweinsberg P, Grant BD, Nance J.
タイトル The P4-ATPase TAT-5 inhibits the budding of extracellular vesicles in C. elegans embryos.
ジャーナル Curr Biol
Abstract BACKGROUND:Cells release extracellular vesicles (ECVs) that can influence differentiation, modulate the immune response, promote coagulation, and induce metastasis. Many ECVs form by budding outwards from the plasma membrane, but the molecules that regulate budding are unknown. In ECVs, the outer leaflet of the membrane bilayer contains aminophospholipids that are normally sequestered to the inner leaflet of the plasma membrane, suggesting a role for lipid asymmetry in ECV budding.
RESULTS:We show that loss of the conserved P4-ATPase TAT-5 causes the large-scale shedding of ECVs and disrupts cell adhesion and morphogenesis in Caenorhabditis elegans embryos. TAT-5 localizes to the plasma membrane and its loss results in phosphatidylethanolamine exposure on cell surfaces. We show that RAB-11 and endosomal sorting complex required for transport (ESCRT) proteins, which regulate the topologically analogous process of viral budding, are enriched at the plasma membrane in tat-5 embryos, and are required for ECV production.
CONCLUSIONS:TAT-5 is the first protein identified to regulate ECV budding. TAT-5 provides a potential molecular link between loss of phosphatidylethanolamine asymmetry and the dynamic budding of vesicles from the plasma membrane, supporting the hypothesis that lipid asymmetry regulates budding. Our results also suggest that viral budding and ECV budding may share common molecular mechanisms.
巻・号 21(23)
ページ 1951-9
公開日 2011-12-6
DOI 10.1016/j.cub.2011.10.040
PII S0960-9822(11)01201-2
PMID 22100064
PMC PMC3237752
MeSH Adenosine Triphosphatases / metabolism* Animals Animals, Genetically Modified Cadherins / metabolism Caenorhabditis elegans / embryology* Caenorhabditis elegans / enzymology Caenorhabditis elegans Proteins / metabolism* Cell Adhesion / physiology Cell Lineage Cell-Derived Microparticles / metabolism Cell-Derived Microparticles / physiology* Embryo, Nonmammalian / enzymology* Histological Techniques Microscopy, Confocal Microscopy, Electron, Transmission Models, Biological* Morphogenesis / genetics Morphogenesis / physiology Neural Cell Adhesion Molecules / metabolism Oligonucleotides / genetics RNA Interference
IF 9.601
引用数 97
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
線虫 C. elegans tat-5 deletion alleles tm1741 and tm1772