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Free keywords:
Animals
Antigens, CD29/metabolism
Biological Transport
Carrier Proteins/metabolism
Caveolae/*metabolism/ultrastructure
Caveolin 1/metabolism
Endocytosis
Keratinocytes/cytology/enzymology
Mice
Microtubules/*enzymology/ultrastructure
Protein Binding
Protein-Serine-Threonine Kinases/deficiency/*metabolism
Signal Transduction
Subcellular Fractions/metabolism
ras GTPase-Activating Proteins/metabolism
Abstract:
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 beta1 integrins and integrin-linked kinase (ILK) in caveolae formation. Mice lacking beta1 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.
