Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins.
Dynamic turnover of integrin cell adhesion molecules to and from the cell surface is central to cell migration. We report for the first time an association between integrins and Rab proteins, which are small GTPases involved in the traffic of endocytotic vesicles. Rab21 (and Rab5) associate with the cytoplasmic domains of alpha-integrin chains, and their expression influences the endo/exocytic traffic of integrins. This function of Rab21 is dependent on its GTP/GDP cycle and proper membrane targeting. Knock down of Rab21 impairs integrin-mediated cell adhesion and motility, whereas its overexpression stimulates cell migration and cancer cell adhesion to collagen and human bone. Finally, overexpression of Rab21 fails to induce cell adhesion via an integrin point mutant deficient in Rab21 association. These data provide mechanistic insight into how integrins are targeted to intracellular compartments and how their traffic regulates cell adhesion.
Pellinen
Teijo
T
VTT Technical Research Centre of Finland, Medical Biotechnology, Turku FIN-20520, Finland.
Arjonen
Antti
A
Vuoriluoto
Karoliina
K
Kallio
Katja
K
Fransen
Jack A M
JA
Ivaska
Johanna
J
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D021381:Protein Transport / Q000502:physiology; D013997:Time Factors; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D019012:Integrin beta1; D049452:Green Fluorescent Proteins; C415145:RAB21 protein, human; D020691:rab GTP-Binding Proteins