title: Arp2/3 complex regulates adipogenesis by controlling cortical actin remodelling.
abstract: Extensive actin cytoskeleton remodelling occurs during adipocyte development. We have previously shown that disruption of stress fibres by the actin-severing protein cofilin is a requisite step in adipogenesis. However, it remains unclear whether actin nucleation and assembly into the cortical structure are essential for adipocyte development. In the present study we investigated the role of cortical actin assembly and of actin nucleation by the actin-related protein 2/3 (Arp2/3) complex in adipogenesis. Cortical actin structure formation started with accumulation of filamentous actin (F-actin) patches near the plasma membrane during adipogenesis. Depletion of Arp2/3 by knockdown of its subunits Arp3 or ARPC3 strongly impaired adipocyte differentiation, although adipogenesis-initiating factors were unaffected. Moreover, the assembly of F-actin-rich structures at the plasma membrane was suppressed and the cortical actin structure poorly developed after adipogenic induction in Arp2/3-deficient cells. Finally, we provide evidence that the cortical actin cytoskeleton is essential for efficient glucose transporter 4 (GLUT4) vesicle exocytosis and insulin signal transduction. These results show that the Arp2/3 complex is an essential regulator of adipocyte development through control of the formation of cortical actin structures, which may facilitate nutrient uptake and signalling events.
authors.affiliation: *Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, #02-02 Helios, 11 Biopolis Way, 138667 Singapore.
authors.forename: Wulin
authors.initials: W
authors.lastname: Yang
authors.affiliation: *Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, #02-02 Helios, 11 Biopolis Way, 138667 Singapore.
authors.forename: Shermaine
authors.initials: S
authors.lastname: Thein
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Lim
authors.affiliation: *Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, #02-02 Helios, 11 Biopolis Way, 138667 Singapore.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ericksen
authors.affiliation: *Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, #02-02 Helios, 11 Biopolis Way, 138667 Singapore.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugii
authors.affiliation: ‡Singapore Institute for Clinical Sciences, 30 Medical Drive, 117609 Singapore.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robinson
authors.affiliation: ║National Creative Research Initiatives Center for Adipose Tissue Remodeling, Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D051377:Actin-Related Protein 2 / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000737:chemistry / Q000378:metabolism*; D051378:Actin-Related Protein 3 / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction
chemical_list: D051377:Actin-Related Protein 2; D051376:Actin-Related Protein 2-3 Complex; D051378:Actin-Related Protein 3; D051275:Glucose Transporter Type 4; D007328:Insulin