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Vol. 54, Issue 3, 431-468, September 2002

Caveolae: From Cell Biology to Animal Physiology

Babak Razani, Scott E. Woodman and Michael P. Lisanti

Department of Molecular Pharmacology, Albert Einstein College of Medicine; and the Division of Hormone-Dependent Tumor Biology, Albert Einstein Cancer Center, New York, New York

I. Introduction
II. Caveolae
    A. Definition and Morphology
    B. Tissue Specificity
    C. Composition and Biochemical Properties
III. The Caveolin Gene Family
    A. The Discovery of Caveolin and Its Relationship to Caveolae
    B. The Other Caveolins (Caveolin-2 and -3)
    C. Structural Properties of the Caveolins
        1. Caveolin Membrane Topology.
        2. Caveolin Oligomerization.
        3. Structural Relationships between the Caveolins.
IV. Caveolar Biogenesis
    A. The Role of Cholesterol
    B. The Role of the Caveolins
V. Functional Significance of Caveolae/Caveolins
    A. Vesicular Transport
        1. Transcytosis.
        2. Endocytosis.
        3. Mechanisms of Endocytosis/Transcytosis.
        4. Potocytosis.
    B. Cellular Cholesterol Homeostasis
        1. The Effect of Cholesterol on Caveolin-1.
        2. Intracellular Transport of de Novo Synthesized cholesterol.
        3. Cholesterol Efflux from Cells.
    C. Signal Transduction Mechanisms
        1. Caveolae As Signalosomes: Compartmentalized Signaling.
        2. The Caveolins As Modulators of Signaling.
        3. Caveolin-2 and -3 As Signaling Modulators.
        4. Signaling Spotlight: Modulation of Endothelial Nitric-Oxide Synthase Function.
        5. Signaling Spotlight: the Dynamic Relationship of G-Protein-Coupled Receptors and Caveolae.
    D. Oncogenes and Tumorigenesis
        1. Caveolae/Caveolins As Targets of Oncogenes.
        2. The Caveolins As Tumor Suppressors.
        3. Relevance to Human Cancers.
    E. Specialized Functions: Caveolin-3 and Muscle Cells
    F. Emerging Functions: Caveolins and Lipid Droplets
VI. Animal Models in the Study of Caveolae and Caveolins
    A. Studies of Caveolin-1-Deficient Mice
        1. Caveolin-1 and Caveolae Biogenesis.
        2. Interactions of Caveolin-1 with the Other Caveolins.
        3. Caveolin-1 and Cellular Proliferation.
        4. Caveolin-1 and Endocytosis.
        5. Caveolin-1 in the Lung.
        6. The Vascular Physiology of Caveolin-1-Deficient Mice.
        7. Caveolin-1 and Lipid Homeostasis.
    B. Studies of Caveolin-2-Deficient Mice
        1. Relationship with Caveolin-1.
        2. The Surprising Role of Caveolin-2 in the Lung.
    C. Studies of Caveolin-3-Deficient Mice
        1. Caveolin-3 and Muscle Disease.
        2. Caveolin-3 and Transverse Tubules.
        3. Caveolin-3 and the Dystrophin-Glycoprotein Complex.
    D. Dominant-Negative Caveolin Mutations in Human Disease
VII. Conclusions and Future Directions
    A. Caveolae and Caveolins
    B. Modifiers of Raft Function
Acknowledgments
References

Among the membrane compartments of a cell, vesicles known as "caveolae" have long defied functional characterization. However, since the identification of a family of proteins termed "caveolins", that form and reside in caveolae, a better understanding has emerged. It is now clear that caveolae do not merely play a singular role in the cell, but are pleiotropic in nature---serving to modulate many cellular functions. The purpose of this review is to explicate what is known about caveolins/caveolae and highlight growing areas of caveolar research.

0031-6997/02/5403-0431$07.00/0
PHARMACOLOGICAL REVIEWS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


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