Changes in integrin expression during adipocyte differentiation

3T3-L1 preadipocytes require cAMP for maximal differentiation. Microarray analysis reveals that the integrins alpha 5 and alpha 6 are coordinately regulated by cAMP. alpha 5 expression is gradually diminished during adipogenesis, whereas alpha 6 is increased. Overexpression of alpha 5 in preadipocytes results in enhanced proliferation and attenuated differentiation. Conversely, alpha 6 overexpression is without effect. The GTPase Rac is normally inhibited during differentiation. However, overexpression of integrin alpha 5 increases Rac activity. Constitutively active but not dominant-negative Rac inhibits differentiation when overexpressed in preadipocytes, implying its role downstream of alpha 5 integrin in maintaining preadipocytes in an undifferentiated state. Moreover, alpha 6 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 alpha 6 in connecting morphogenesis with signaling processes leading to terminal differentiation.