a role for phospholipase d3 in myotube formation磷脂酶的作用d3肌管形成.pdfVIP

A Role for Phospholipase D3 in Myotube Formation 1 2,3 1,2,3 Mary Osisami , Wahida Ali , Michael A. Frohman * 1 Center for Developmental Genetics, Graduate Program in Genetics, Stony Brook University, Stony Brook, New York, United States of America, 2 Graduate Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, United States of America, 3 Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America Abstract Phospholipase D3 (PLD3) is a non-classical, poorly characterized member of the PLD superfamily of signaling enzymes. PLD3 is a type II glycoprotein associated with the endoplasmic reticulum, is expressed in a wide range of tissues and cells, and undergoes dramatic upregulation in neurons and muscle cells during differentiation. Using an in vitro skeletal muscle differentiation system, we define the ER-tethering mechanism and report that increased PLD3 expression enhances myotube formation, whereas a putatively dominant-negative PLD3 mutant isoform reduces myotube formation. ER stress, which also enhances myotube formation, is shown here to increase PLD3 expression levels. PLD3 protein was observed to localize to a restricted set of subcellular membrane sites in myotubes that may derive from or constitute a subdomain of the endoplasmic reticulum. These findings suggest that PLD3 plays a role in myogenesis during myotube formation, potentially in the events surrounding ER reorganization. Citation: Osisami M, Ali W, Frohman MA (2012) A Role for Phospholipase D3 in Myotube Formation. PLoS ONE 7(3): e33341. doi:10.1371/journal.pone.0033341 Editor: Daniel Sanchis, Universitat de Lleida – IRBLLEIDA, Spain Received September 15, 2011; Ac