title: A role for phospholipase D3 in myotube formation.
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.
authors.affiliation: Center for Developmental Genetics, Graduate Program in Genetics, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Osisami
authors.forename: Wahida
authors.initials: W
authors.lastname: Ali
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000502:physiology*; D041681:NIH 3T3 Cells; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D005090:Exodeoxyribonucleases
chemical_list: D017931:DNA Primers; D010739:Phospholipase D; C542157:Pld3 protein, mouse; D005090:Exodeoxyribonucleases