Changes in integrin expression during adipocyte differentiation.
3T3-L1 preadipocytes require cAMP for maximal differentiation. Microarray analysis reveals that the integrins alpha5 and alpha6 are coordinately regulated by cAMP. alpha5 expression is gradually diminished during adipogenesis, whereas alpha6 is increased. Overexpression of alpha5 in preadipocytes results in enhanced proliferation and attenuated differentiation. Conversely, alpha6 overexpression is without effect. The GTPase Rac is normally inhibited during differentiation. However, overexpression of integrin alpha5 increases Rac activity. Constitutively active but not dominant-negative Rac inhibits differentiation when overexpressed in preadipocytes, implying its role downstream of alpha5 integrin in maintaining preadipocytes in an undifferentiated state. Moreover, alpha6 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 alpha6 in connecting morphogenesis with signaling processes leading to terminal differentiation.
Liu
Jun
J
Department of Internal Medicine, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
DeYoung
Stephanie M
SM
Zhang
Ming
M
Zhang
Mei
M
Cheng
Alan
A
Saltiel
Alan R
AR
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D046228:Microarray Analysis; D018613:Microscopy, Confocal; D011509:Proteoglycans / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D015415:Biomarkers; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D039482:Integrin alpha5; D039503:Integrin alpha6; D007546:Isoquinolines; D007797:Laminin; D011509:Proteoglycans; D013449:Sulfonamides; C059485:matrigel; D049452:Green Fluorescent Proteins; D003907:Dexamethasone; D003094:Collagen; D000242:Cyclic AMP; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide