A new paradigm for membrane‐organizing and ‐shaping scaffolds

Abstract

The clathrin, COPI and COPII scaffolds are paradigm vesicle coats in membrane trafficking. Recent advances in our understanding of the caveolar coat have generated a new paradigm. It represents those membrane coats, where a considerable part of the protein component is lipid modified, and integrated into the cytosolic leaflet of the vesicle membrane by a hairpinlike hydrophobic structure. Such coat proteins are permanently associated with membranes, and form oligomers early after synthesis. These oligomers assemble into a coat that has high affinity for particular lipids, creating lipid microdomains within the membrane. The combined protein-lipid structure should be considered as the scaffold that entraps ligands, either through affinity with the protein or with the lipid component, and that has the ability to shape membranes. Besides scaffolds assembled by caveolins, scaffolds assembled by reticulons and PHB domain-containing proteins such as the reggie/flotillin proteins fit this paradigm.

Phosphoproteomic Analysis Reveals Regulatory Mechanisms at the Kidney Filtration Barrier

“…As previously published, stomatin forms multimeric megadalton complexes ( Figure 7A). 38 Consistent with the results obtained in silico, stomatin showed an increased multimerization when the phosphomimicking mutation S161D was present (lack of low molecular mass complexes, with a molecular mass,1000 kDa) ( Figure 7A). In contrast and consistent with the simulations, podocin showed a lower multimeric complex when the T234D mutation was introduced ( Figure 7B).…”

Molecular mechanisms of clathrin-independent endocytosis

“…This implies that budding of flotillin microdomains, similar to that of caveolin-containing caveolae, might be a highly regulated process, and that flotillin-or caveolin-positive vesicles are not likely to be abundant in the cytoplasm (Bauer and Pelkmans, 2006;Thomsen et al, 2002). Flotillins, similar to caveolins, have been reported to bind to Src-family kinases and, in both cases, mutation of specific tyrosine residues alters the subcellular distribution of these proteins (Neumann-Giesen et al, 2007;Stuermer et al, 2001;Sverdlov et al, 2007).…”

β-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release

“…Caveolae are cholesterol-and sphingolipid-enriched membrane invaginations that are abundant in mature smooth muscle cells (Cohen et al, 2004;Gosens et al, 2006a;Sharma et al, 2008). Caveolin-1 is the primary structural caveolae protein in smooth muscle, and forms a hetero-oligomeric network with caveolin-2 along the inner leaflet of the plasma membrane (Bauer and Pelkmans, 2006;Das et al, 1999). Caveolae and caveolin-1 have a key role in orchestrating activation of pathways that underpin cell proliferation, migration, and contraction (Cohen et al, 2004;Halayko and Stelmack, 2005).…”