Regulation of intracellular signaling and function by caveolin

Abstract

Caveolae, flask-like invaginations of the plasma membrane, were discovered nearly 60 years ago. Originally regarded as fixation artifacts of electron microscopy, the functional role for these structures has taken decades to unravel. The discovery of the caveolin protein in 1992 (by the late Richard G.W. Anderson) accelerated progress in defining the contribution of caveolae to cellular physiology and pathophysiology. The three isoforms of caveolin (caveolin-1, -2, and -3) are caveolae-resident structural and scaffolding proteins that are critical for the formation of caveolae and their localization of signaling entities. A PubMed search for "caveolae" reveals ∼280 publications from their discovery in the 1950s to the early 1990s, whereas a search for "caveolae or caveolin" after 1990, identifies ∼7000 entries. Most work on the regulation of biological responses by caveolae and caveolin since 1990 has focused on caveolae as plasma membrane microdomains and the function of caveolin proteins at the plasma membrane. By contrast, our recent work and that of others has explored the localization of caveolins in multiple cellular membrane compartments and in the regulation of intracellular signaling. Cellular organelles that contain caveolin include mitochondria, nuclei and the endoplasmic reticulum. Such intracellular localization allows for a complexity of responses to extracellular stimuli by caveolin and the possibility of novel organelle-targeted therapeutics. This review focuses on the impact of intracellular localization of caveolin on signal transduction and cell regulation.

Caveolae and cancer: A new mechanical perspective

“…[6,7] There is, however, some debate on the relevance of these interactions and the mechanisms by which caveolae and/or caveolins may control intracellular signaling. [8] The modulation of cell signaling by caveolae and/or Cav1 could be one of the mechanisms by which caveolae play a role in cell transformation and tumor progression.…”

CAVEOLINA-1 implicaciones fisiológicas y patológicas

“…At the cellular level, various cellular components containing cav-1 have been determined (7) , among which we include: cytoplasmic membrane, Golgi apparatus, mitochondria (8) , endoplasmic reticulum, membrane vesicles (9) and nucleus (10) . Fig.…”

“…Caveolae structure: when cav is inserted in the lipid layers of the cell membrane, invaginations are formed, leading to the three-dimensional structure that makes up the caveolae. A cav-1 deficiency at the mitochondrial level triggers a series of disorders including lipid dystrophy, cancer, diabetes, muscular dystrophy, heart disease and pulmonary fibrosis (7) . Some studies suggest that the role of cav-1 as a cholesterol transporter and homeostasis regulator would affect mitochondrial function.…”

“…In turn, cav-1-dependent endocytosis regulates cell attachment by internalizing integrins and components of tight junctions (occludens) and adhesion. Additionally, the mediator function of transcytosis allows for the transport of albumin-conjugated nutrients, fatty acids and hormones through the endothelium (7) . At the nuclear level, cav-1 acts as a genetic regulator and tumor suppressor.…”

“…Their activity is highly dependent on the cellular context in which they are found, them being positive and negative regulators of cell signaling both inside and outside the caveola. This set of proteins and lipids accumulated in micro membrane domains can communicate a rapid, specific and amplified signal cascade, cell proliferation, apoptosis and migration (7) .…”