Changes in integrin expression during adipocyte differentiation

3T3-L1 preadipocytes require cAMP for maximal differentiation. Microarray analysis reveals that the integrins α5 and α6 are coordinately regulated by cAMP. α5 expression is gradually diminished during adipogenesis, whereas α6 is increased. Overexpression of α5 in preadipocytes results in enhanced proliferation and attenuated differentiation. Conversely, α6 overexpression is without effect. The GTPase Rac is normally inhibited during differentiation. However, overexpression of integrin α5 increases Rac activity. Constitutively active but not dominant-negative Rac inhibits differentiation when overexpressed in preadipocytes, implying its role downstream of α5 integrin in maintaining preadipocytes in an undifferentiated state. Moreover, α6 integrin is critically involved in clustering growth-arrested preadipocytes on basement membrane Matrigel. Perturbation of such clustering enhances Rho activity and promotes growth-arrested preadipocytes to reenter the cell cycle. These findings demonstrate a role for integrin α6 in connecting morphogenesis with signaling processes leading to terminal differentiation.