Tropomodulin3 as the link between insulin-activated AKT2 and cortical actin remodeling in preparation of GLUT4 exocytosis.
It is well established that insulin-induced remodeling of actin filaments into a cortical mesh is required for insulin-stimulated GLUT4 exocytosis. Akt2 and its downstream effectors play a pivotal role in mediating the translocation and membrane fusion of GLUT4-storage vesicle (GSV). However, the direct downstream effector underlying the event of cortical actin reorganization has not been elucidated. In a recent study in Nature Communications, (1) Lim et al identify Tropomodulin3 (Tmod3) as a downstream target of the Akt2 kinase and describe the role of this pointed-end actin-capping protein in regulating insulin-dependent exocytosis of GSVs in adipocytes through the remodeling of the cortical actin network. Phosphorylation of Tmod3 by Akt2 on Ser71 modulates insulin-induced actin remodeling, a key step for GSV fusion with the plasma membrane (PM). Furthermore, the authors establish Tm5NM1 (Tpm3.1 in new nomenclature) (2) as the cognate tropomyosin partner of Tmod3, and an essential role of Tmod3-Tm5NM1 interaction for GSV exocytosis and glucose uptake. This study elucidates a novel effector of Akt2 that provides a direct mechanistic link between Akt2 signaling and actin reorganization essential for vesicle fusion, and suggests that a subset of actin filaments with specific molecular compositions may be dedicated for the process of vesicle fusion.
a Laboratory of Metabolic Medicine; Singapore Bioimaging Consortium ; Agency for Science; Technology and Research ; Singapore , Republic of Singapore.
Chun-Yan
CY
Lim
Weiping
W
Han
D000199:Actins / Q000378:metabolism*; D000818:Animals; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051348:Tropomodulin / Q000378:metabolism*
D000199:Actins; D051275:Glucose Transporter Type 4; D007328:Insulin; D051348:Tropomodulin; D051057:Proto-Oncogene Proteins c-akt
Akt2; GLUT4; Tm5NM1; Tmod3; cortical actin; exocytosis