the tip30 protein complex, arachidonic acid and coenzyme a are required for vesicle membrane fusiontip30蛋白质复杂,花生四烯酸和辅酶a所需泡膜融合.pdfVIP

The TIP30 Protein Complex, Arachidonic Acid and Coenzyme A Are Required for Vesicle Membrane Fusion 1,2 1,3 1 2 1 Chengliang Zhang , Aimin Li , Shenglan Gao , Xinchun Zhang , Hua Xiao * 1 Department of Biomedical and Integrative Physiology, Michigan State University, East Lansing, Michigan, United States of America, 2 Genetics Program, Michigan State University, East Lansing, Michigan, United States of America, 3 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China 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 f