PKCε regulates contraction-stimulated GLUT4 traffic in skeletal muscle cells

✍ Scribed by Wenyan Niu; Philip J. Bilan; Junna Yu; Jing Gao; Shlomit Boguslavsky; Jonathan D. Schertzer; Guilan Chu; Zhi Yao; Amira Klip

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 294 KB
• Volume: 226
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.22320

✦ Synopsis

Abstract

The signaling pathways that stimulate glucose uptake in response to muscle contraction are not well defined. Recently, we showed that carbachol, an acetylcholine analog, stimulates contraction of C2C12 myotube cultures and the rapid arrival of myc‐epitope tagged GLUT4 glucose transporters at the cell surface. Here, we explore a role for protein kinase C (PKC) in regulating GLUT4 traffic. Cell surface carbachol‐induced GLUT4__myc__ levels were partly inhibited by the conventional/novel PKC inhibitors GF‐109203X, Gö6983, and Ro‐31‐8425 but not by the conventional PKC inhibitor Gö6976. C2C12 myotubes expressed several novel isoforms of PKC mRNA with PKCδ and PKCε in greater abundance. Carbachol stimulated phosphorylation of PKC isoforms and translocation of PKCδ and PKCε to membranes within 5 min. However, only a peptidic inhibitor of PKCε translocation (myristoylated‐EAVSLKPT), but not one of PKCδ (myristoylated‐SFNSYELGSL), prevented the GLUT4__myc__ response to carbachol. Significant participation of PKCε in the carbachol‐induced gain of GLUT4__myc__ at the surface of C2C12 myotubes was further supported through siRNA‐mediated PKCε protein knockdown. These findings support a role for novel PKC isoforms, especially PKCε, in contraction‐stimulated GLUT4 traffic in muscle cells. J. Cell. Physiol. 226: 173–180, 2010. © 2010 Wiley‐Liss, Inc.