A role for 1-acylglycerol-3-phosphate-O-acyltransferase-1 in myoblast differentiation.
AGPAT isoforms catalyze the acylation of lysophosphatidic acid (LPA) to form phosphatidic acid (PA). AGPAT2 mutations are associated with defective adipogenesis. Muscle and adipose tissue share common precursor cells. We investigated the role of AGPAT isoforms in skeletal muscle development. We demonstrate that small interference RNA-mediated knockdown of AGPAT1 expression prevents the induction of myogenin, a key transcriptional activator of the myogenic program, and inhibits the expression of myosin heavy chain. This effect is rescued by transfection with AGPAT1 but not AGPAT2. Knockdown of AGPAT2 has no effect. The regulation of myogenesis by AGPAT1 is associated with alterations on actin cytoskeleton. The role of AGPAT1 on actin cytoskeleton is further supported by colocalization of AGPAT1 to areas of active actin polymerization. AGPAT1 overexpression was not associated with an increase in PA levels. Our observations strongly implicate AGPAT1 in the development of skeletal muscle, specifically to terminal differentiation. These findings are linked to the regulation of actin cytoskeleton.
Subauste
Angela R
AR
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0678, USA. asubaust@umich.edu
Elliott
Brandon
B
Das
Arun K
AK
Burant
Charles F
CF
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000502:physiology*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D051379:Mice; D032446:Myoblasts / Q000166:cytology*; D013347:Subcellular Fractions / Q000201:enzymology
D000199:Actins; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase