title: The TIP30 protein complex, arachidonic acid and coenzyme A are required for vesicle membrane fusion.
abstract: Efficient membrane fusion has been successfully mimicked in vitro using artificial membranes and a number of cellular proteins that are currently known to participate in membrane fusion. However, these proteins are not sufficient to promote efficient fusion between biological membranes, indicating that critical fusogenic factors remain unidentified. We have recently identified a TIP30 protein complex containing TIP30, acyl-CoA synthetase long-chain family member 4 (ACSL4) and Endophilin B1 (Endo B1) that promotes the fusion of endocytic vesicles with Rab5a vesicles, which transport endosomal acidification enzymes vacuolar (H⁺)-ATPases (V-ATPases) to the early endosomes in vivo. Here, we demonstrate that the TIP30 protein complex facilitates the fusion of endocytic vesicles with Rab5a vesicles in vitro. Fusion of the two vesicles also depends on arachidonic acid, coenzyme A and the synthesis of arachidonyl-CoA by ACSL4. Moreover, the TIP30 complex is able to transfer arachidonyl groups onto phosphatidic acid (PA), producing a new lipid species that is capable of inducing close contact between membranes. Together, our data suggest that the TIP30 complex facilitates biological membrane fusion through modification of PA on membranes.
authors: Department of Biomedical and Integrative Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors: Chengliang
authors: C
authors: Zhang
authors: Aimin
authors: A
authors: Li
authors: Shenglan
authors: S
authors: Gao
authors: Xinchun
authors: X
authors: Zhang
authors: Hua
authors: H
authors: Xiao
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000215:Acylation; D000217:Acyltransferases / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D003065:Coenzyme A / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008561:Membrane Fusion; D010712:Phosphatidic Acids / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D010712:Phosphatidic Acids; D011994:Recombinant Proteins; D014157:Transcription Factors; D016718:Arachidonic Acid; D000217:Acyltransferases; D000123:Acetyltransferases; C111246:HTATIP2 protein, human; C018764:2-acylglycerophosphate acyltransferase; D020696:rab5 GTP-Binding Proteins; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D003065:Coenzyme A