Diacylglycerol Kinase-ζ Localization in Skeletal Muscle Is Regulated by Phosphorylation and Interaction with Syntrophins

• DOI: 10.1091/mbc.e03-03-0190
• Publication Date: 2003-08-11T22:37:42Z
• Authors: Hanan Abramovici; Angela B. Hogan; Christopher Obagi; Matthew K. Topham; Stephen H. Gee
• Keywords: Sarcolemma

Syntrophins are scaffolding proteins that link signaling molecules to dystrophin and the cytoskeleton. We previously reported syntrophins interact with diacylglycerol kinase-ζ (DGK-ζ), which phosphorylates yield phosphatidic acid. Here, we show DGK-ζ form a complex in skeletal muscle whose translocation from cytosol plasma membrane is regulated by protein kinase C-dependent phosphorylation of MARCKS domain. mutants do not bind were mislocalized, an activated mutant this sort induced atypical changes actin cytoskeleton, indicating important for localizing regulating its activity. Consistent role organization, colocalized filamentous (F)-actin Rac lamellipodia ruffles. Moreover, extracellular signal-related kinase-dependent association In adult muscle, was on sarcolemma concentrated at neuromuscular junctions (NMJs), whereas type IIB fibers it found exclusively NMJs. reduced dystrophin-deficient mdx mouse myofibers but specifically retained NMJs, sarcolemmal synaptic localization DGK-ζ. Together, our findings suggest localize complexes specialized domains cells, may be critical proper control lipid-signaling pathways organization. dystrophic mislocalized cause abnormal cytoskeletal contribute disease pathogenesis.