unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes非传统分泌组织转谷氨酰胺酶需要phospholipid-dependent交付到回收核内体.pdfVIP

Unconventional Secretion of Tissue Transglutaminase Involves Phospholipid-Dependent Delivery into Recycling Endosomes 1,2 2,3 6 7 1,2,4,5 Evgeny A. Zemskov , Irina Mikhailenko , Ru-Ching Hsia , Liubov Zaritskaya , Alexey M. Belkin * 1 Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 2 Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 3 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 4 Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 5 Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 6 Core Imaging Facility, University of Maryland Dental School, Baltimore, Maryland, United States of America, 7 Applied and Developmental Research Support Program, Science Applications International Corporation, Frederick, Maryland, United States of America Abstract Although endosomal compartments have been suggested to play a role in unconventional protein secretion, there is scarce experimental evidence for such involvement. Here we report that recycling endosomes are essential for externalization of cytoplasmic secretory protein tissue transglutaminase (tTG). The de novo synthesized cytoplasmic tTG does not follow the classical ER/Golgi-dependent secretion pathway, but is targeted to perinuclear recycling endosomes, and is delivered inside these vesicles prior to externalization. On its