Ca²⁺induces clustering of membrane proteins in the plasma membrane via electrostatic interactions

Abstract

Membrane proteins and membrane lipids are frequently organized in submicron-sized domains within cellular membranes. Factors thought to be responsible for domain formation include lipid-lipid interactions, lipid-protein interactions and protein-protein interactions. However, it is unclear whether the domain structure is regulated by other factors such as divalent cations. Here, we have examined in native plasma membranes and intact cells the role of the second messenger Ca 2 þ in membrane protein organization. We find that Ca 2 þ at low micromolar concentrations directly redistributes a structurally diverse array of membrane proteins via electrostatic effects. Redistribution results in a more clustered pattern, can be rapid and triggered by Ca 2 þ influx through voltage-gated calcium channels and is reversible. In summary, the data demonstrate that the second messenger Ca 2 þ strongly influences the organization of membrane proteins, thus adding a novel and unexpected factor that may control the domain structure of biological membranes.

Differential Interaction of Tomosyn with Syntaxin and SNAP25 Depends on Domains in the WD40 β-Propeller Core and Determines Its Inhibitory Activity

“…(Fig. 1C, p Ͼ 0.05) and also similar to the value calculated for syntaxin previously (17,27). This finding, together with the Förster (fluorescence) resonance energy transfer (FRET) between syntaxin and tomosyn (26), suggests that at the PM tomosyn moves with a dynamics similar to that of syntaxin.…”

Role of cholesterol in SNARE-mediated trafficking on intracellular membranes

“…In addition, factors that promote SNARE clustering at the plasma membrane include their partitioning into cholesterol-enriched membrane rafts, competition with cholesterol for solvation by bulk lipids, and electrostatic protein-lipid interactions. Furthermore, the clustering of plasma-membrane-associated proteins, including the SNAREs listed above, might be promoted by protein-protein interactions ( Zilly et al, 2011), homotypic interactions between the SNARE motifs (Sieber et al, 2006), heterotypic proteinprotein interactions (Yang et al, 2006) and anchoring to the cortical cytoskeleton (Low et al, 2006;Torregrosa-Hetland et al, 2011). Nevertheless, the extent to which cholesterol-mediated plasma membrane clustering of SNAREs contributes to their overall distribution remains unclear.…”

The reserve pool of synaptic vesicles acts as a buffer for proteins involved in synaptic vesicle recycling

“…Although our results do not demonstrate that protein buffering is the only function of the nonreleasing vesicles, they do indicate that these vesicles act precisely as a buffer, according to its definition: they bind and enrich proteins and are able to release them upon activity, which ultimately prevents the diffusion and loss of proteins from the synapses during periods of inactivity (note that the reserve vesicles themselves remain "inactive" throughout, i.e., they do not exocytose). Calcium may trigger the protein unbinding from vesicles through second messenger interactions; however, it is interesting to note that a direct effect of calcium on the clustering of several unrelated plasma membrane proteins (via electrostatic interactions) has been recently reported (16).…”