Integrin-linked kinase controls microtubule dynamics required for plasma membrane targeting of caveolae.
Caveolae are specialized compartments of the plasma membrane that are involved in signaling, endocytosis, and cholesterol transport. Their formation requires the transport of caveolin-1 to the plasma membrane, but the molecular mechanisms regulating the transport are largely unknown. Here, we identify a critical role for adhesion-mediated signaling through β1 integrins and integrin-linked kinase (ILK) in caveolae formation. Mice lacking β1 integrins or ILK in keratinocytes have dramatically reduced numbers of plasma membrane caveolae in vivo, which is due to impaired transport of caveolin-1-containing vesicles along microtubules (MT) to the plasma membrane. Mechanistically, ILK promotes the recruitment of the F-actin binding protein IQGAP1 to the cell cortex, which, in turn, cooperates with its effector mDia1 to locally stabilize MTs and to allow stable insertion of caveolae into the plasma membrane. Our results assign an important role to the integrin/ILK complex for caveolar trafficking to the cell surface.
Department of Molecular Medicine, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. wickstroem@age.mpg.de
Sara A
SA
Wickström
Anika
A
Lange
Michael W
MW
Hess
Julien
J
Polleux
Joachim P
JP
Spatz
Marcus
M
Krüger
Kristian
K
Pfaller
Armin
A
Lambacher
Wilhelm
W
Bloch
Matthias
M
Mann
Lukas A
LA
Huber
Reinhard
R
Fässler
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism* / Q000648:ultrastructure; D051242:Caveolin 1 / Q000378:metabolism; D004705:Endocytosis; D000080865:Formins; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008870:Microtubules / Q000201:enzymology* / Q000648:ultrastructure; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D000099200:Scaffold Protein ILK
D002352:Carrier Proteins; D051242:Caveolin 1; D000080865:Formins; D019012:Integrin beta1; D017346:Protein Serine-Threonine Kinases; D020703:ras GTPase-Activating Proteins; D000099200:Scaffold Protein ILK; C491464:Diap1 protein, mouse; C101203:IQ motif containing GTPase activating protein 1