Actin Filament Formation in Myofibrils and Cell Protrusions Regulated by Signal Transduction
Actin filaments play crucial roles in a wide variety of cellular functions in all eukaryotic cell types. Typically, they are essential for muscle contraction as thin filaments of contractile myofibrils and for cell migration as components of stress fibers, filopodia, and lamellipodia. Specific actin nucleation factors and elongation factors participate in actin filament formation depending on cell types and actin filament-containing structures. The formation of actin filaments as well as their dynamics is regulated by complicated signaling mechanisms. We summarize here molecular and signaling mechanisms of actin filament formation of myofibrils and cytonemes, a special type of cell protrusions involved in intercellular signaling, focusing on our recent research on these subjects. Myofibrils are well-known muscle contractile structures consisting mainly of actin and myosin filaments. However, molecular and signaling mechanisms of their formation have been obscure. We have elucidated the mechanisms of skeletal muscle myofibrillar actin filament formation induced by insulin-like growth factor 1 (IGF-1). IGF-1-stimulated phosphatidylinositol 3-kinase–Akt signaling induces the formation of the nebulin–N-WASP complex, which nucleates actin and forms actin filaments from the Z-bands. We have also examined the mechanisms of myofibrillar actin filament formation in cardiac muscle, in which nebulin is absent. On the other hand, cytonemes represent novel highly efficient, long-range intercellular signaling machinery. We have found that fibroblast growth factor signaling causes activation of RhoD, which in turn activates mDia3C to form actin filaments leading to cytoneme formation.
KeywordsActin filament Myofibril Skeletal muscle Cardiac muscle IGF-1 signaling N-WASP Cell protrusion Cytoneme Intercellular signaling RhoD
Our study is supported by Grants-in-Aid for Scientific Research on Innovative Areas (23117506 and 25117706) from the Ministry of Education, Culture, Sports, Science, and Technology; Grants-in-Aid for Scientific Research (B) (23300144), for Young Scientists (B) (24770118), and for Challenging Exploratory Research (25670104) from Japan Society for the Promotion of Science; and Intramural Research Grant (23–5) for Neurological and Psychiatric Disorders of National Center of Neurology and Psychiatry.
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