Tetraspanins regulate the protrusive activities of cell membrane

Abstract

Tetraspanins have gained increased attention due to their functional versatility. But the universal cellular mechanism that governs such versatility remains unknown. Herein we present the evidence that tetraspanins CD81 and CD82 regulate the formation and/or development of cell membrane protrusions. We analyzed the ultrastructure of the cells in which a tetraspanin is either overexpressed or ablated using transmission electron microscopy. The numbers of microvilli on the cell surface were counted, and the radii of microvillar tips and the lengths of microvilli were measured. We found that tetraspanin CD81 promotes the microvillus formation and/or extension while tetraspanin CD82 inhibits these events. In addition, CD81 enhances the outward bending of the plasma membrane while CD82 inhibits it. We also found that CD81 and CD82 proteins are localized at microvilli using immunofluorescence. CD82 regulates microvillus morphogenesis likely by altering the plasma membrane curvature and/or the cortical actin cytoskeletal organization. We predict that membrane protrusions embody a common morphological phenotype and cellular mechanism for, at least some if not all, tetraspanins. The differential effects of tetraspanins on microvilli likely lead to the functional diversification of tetraspanins and appear to correlate with their functional propensity.

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

“…In relation to the cell surface topology, tetraspanins regulate membrane microextrusions (Fig. 2) [79,80]. Forced expression of CD82 reduces the formation and development of microextrusions, while Cd82 ablation potentiates them, probably by altering membrane bending and/or membranecytoskeleton interaction [14,55].…”

Impact of lysosome status on extracellular vesicle content and release

“…While most tetraspanin proteins are predominantly present on the plasma membrane, CD63 is mostly present on the surface of endosomes. It has been reported that CD63 has a tendency to generate large protein domains on the inner surface of late endosomes that can change the physical properties of the membrane in a manner that encourages invagination (Piccin, Murphy et al 2007, Bari, Guo et al 2011). An additional mechanism for exosome biogenesis involves the accumulation of the bioactive lipid ceramide in the endosomal membrane (Trajkovic, Hsu et al 2008).…”

Glial M6B stabilizes the axonal membrane at peripheral nodes of Ranvier

“…How does the presence of M6B on the Schwann cell microvilli affect the structure of the underlying axonal membrane? Tetraspanin proteins are involved in the formation of various tubular cell membrane structures including microvilli (Singethan & Schneider-Schaulies, 2008;Bari et al, 2011). They regulate cell morphogenesis by altering the membrane curvature, as well as by mediating membrane-dependent cytoskeletal reorganization.…”