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. [Display omitted] ► Formation of plasma membrane caveolae in keratinocytes requires β1 integrin and ILK ► β1 integrin/ILK recruit IQGAP1/mDia to nascent focal adhesions at the cell cortex ► IQGAP1/mDia stabilizes MTs and promotes caveolin trafficking to the plasma membrane ► Thus, the ILK/mDia/MT pathway drives caveolin availability for caveolae formation