Membrane microdomains and proteomics: Lessons from tetraspanin microdomains and comparison with lipid rafts

Abstract

Biological membranes are compartmentalized into microdomains that exhibit particular lipid and protein compositions. Membrane microdomains, such as tetraspanin-enriched microdomains and lipid rafts, have been suggested to play a role in a variety of physiological and pathological processes. Therefore, the characterization of the protein compositions of these microdomains, which is the focus of this review, appears to be a crucial step to better understanding their function. Proteomics has recently allowed the characterization of tetraspanin-enriched microdomains in colon cancer cells. This demonstrated the presence of different categories of membrane proteins and suggested a variation in the composition of tetraspanin-enriched microdomains during tumor progression. On the other hand, proteomics has permitted the identification of hundreds of proteins in lipid rafts of different origins. However, the diversity of methodologies in sample preparation and of strategies in protein identification led to a broad variability in the data obtained. These methodological issues are discussed. Moreover, proteomics has revealed that different sets of proteins were present in tetraspanin-enriched microdomains as compared with lipid rafts, strengthening the idea that these microdomains are distinct structures.

Cell Surface Tetraspanin Tspan8 Contributes to Molecular Pathways of Exosome-Induced Endothelial Cell Activation

“…The recovery of membrane microdomains in exosomes is of particular interest with respect to tetraspanins, which organize clusters of tetraspanins, additional transmembrane proteins, and membrane-proximal signaling proteins, such as integrins, G protein-coupled receptors, proteases, and protein kinase C (10,(18)(19)(20). Prominent Tspan8 partners are CD13, EWI-F, intersectin-2, EpCAM, CD49c, and CD104 (21).…”

CD49d blockade by natalizumab therapy in patients with multiple sclerosis increases immature B-lymphocytes

“…Integrins are known to interact strongly with other adhesion molecules on the cell's surface, especially via lipid rafts. 7 Although CD49d is the specific target of natalizumab, and therefore is logically modulated on the cells, our results suggest that this disruption of one integrin may also alter the expression of other adhesion molecules. The net result could therefore be, as expected, a defective stimulation potential of B and T cells, along with decreased migration capacities across the blood-brain barrier.…”

Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling

“…They are considered as physically Journal of Cell Science 123 (5) and functionally distinct from lipid rafts (Boucheix et al, 2004;Hemler, 2003) but they depend at least in part on lipids, including gangliosides (GM) and cholesterol (Charrin et al, 2003b). It has been shown that CD82 increases surface expression of several gangliosides and associates with and regulates cholesterol-rich microdomains (Charrin et al, 2003b;Delaguillaumie et al, 2004;Hemler, 2003;Le Naour et al, 2006). Moreover, cholesterol has a role in the diffusion of EGFR since its depletion led to almost complete confinement of the receptors (Orr et al, 2005).…”