Читать книгу Recent Advances in the Pathogenesis and Treatment of Kidney Diseases - Группа авторов - Страница 11

Caveolae are 50–80 nm, flask-shaped, membrane invaginations that were originally identified as very small pit-like depressions on the cell membrane of microvilli in 1955 [1]. Caveolae are primarily located on vascular endothelial cells, smooth muscle cells, cardiomyocytes, and adipocytes; they are enriched with cholesterol, sphingolipids, and glycolipids, and are structured by scaffolding proteins known as caveolin. There are three caveolin proteins encoded by independent genes, which are identified as caveolin-1 (Cav-1), caveolin-2, and caveolin-3. Cav-1 and caveolin-2 are co-expressed on a variety of cells, while caveolin-3 is solely expressed by muscle cells [2, 3]. Cav-1 is expressed as 2 isoforms: Cav-1α contains 178 amino acids and Cav-1β contains 147 amino acids, lacking the N-terminal 31 amino acids of Cav-1α. These isoforms arise from 2 different mRNA transcripts of the same gene. Both isoforms of Cav-1 are membrane proteins with a 33-amino-acid hydrophobic domain that constitutes a hairpin loop; the N-termini and C-termini extend into the cytoplasm. Cav-1 proteins assemble as disk-shaped oligomers around the scaffolding domain and are anchored by a portion of the palmitoylated C-terminal within the cell membrane [2, 3]. The roles of caveolae are diverse and comprise adjustment of endothelial nitric oxide synthesis and calcium signaling; regulation of intracellular signal transduction, including receptors, such as G-protein coupled receptors, epidermal growth factor receptors, insulin receptors, platelet-derived growth factor receptors (PDGF-R), vascular endothelial growth factor receptors, activin receptor-like kinase, transforming growth factor-β, ras-mitogen activated protein kinase, Src family tyrosine kinases, various forms of protein kinase A, and various forms of protein kinase C (Table 1) [4, 5]; and to internalize and transport cholesterol, proteins, insulin, and toxins that play pivotal roles in a variety of diseases (e.g., viral infections, inflammation, cancer, cardiovascular disease, atherosclerosis, myopathies, and diabetes [6–9]). In the kidney, caveolae are expressed by glomerular endothelial cells (Fig. 1a), epithelial cells (Fig. 1a), mesangial cells, and tubular epithelial cells. However, the specific roles of caveolae in the kidney cells are not yet known.