APPL1 promotes glucose uptake in response to mechanical stretch via the PKC zeta-non-muscle myosin IIa pathway in C2C12 myotubes

作者：Saito Tsugumichi^*; Okada Shuichi; Shimoda Yoko; Tagaya Yuko; Osaki Aya; Yamada Eijiro; Shibusawa Ryo; Nakajima Yasuyo; Ozawa Atsushi; Satoh Tetsurou; Mori Masatomo; Yamada Masanobu

来源：Cellular Signalling, 2016, 28(11): 1694-1702.

DOI：10.1016/j.cellsig.2016.07.010

• APPL1
• Mechanical stretch
• Glucose uptake
• PKC zeta
• Non-muscle myosin IIa

Expression of adaptor protein, phosphotyrosine interaction, pleckstrin homology domain, and leucine zipper containing 1 (APPL1) promoted glucose transporter 4 (GLUT4) translocation and glucose uptake in adipose and muscle tissues in response to stimulation with insulin, adiponectin, or exercise. In response to mechanical stretch, knockdown of APPL1 in C2C12 myotubes suppressed glucose uptake. APPL1-induced increased glucose uptake was mediated by protein kinase C (PKC) zeta but not AKT, AMPK, or calmodulin-dependent protein kinase. In myotubes overexpressing APPL1,PKC zeta was phosphorylated and translocated to the plasma membrane (PM) in response to mechanical stretch. Phosphorylated PKC zeta co-immunoprecipitated with protein phosphatase 2A (PP2A) under basal conditions, but dissociated upon myotube stretching. Moreover, stretch-induced phosphorylated PKC zeta co-immunoprecipitated with non-muscle myosin Ha. Blebbistatin, an inhibitor of myosin II ATPase activity, suppressed APPL1-mediated stretch-induced glucose uptake and PKC zeta translocation. Taken together these data demonstrate that in response to mechanical stretch, APPL1 enhances glucose uptake by modulating the activation and localization of PKC zeta, as well as its functional interaction with both PP2A and myosin Ila. These findings support a new function for non-muscle myosin Ha in differentiated myotubes.

• 出版日期2016-11