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

• Published in: The EMBO journal Vol. 30; no. 7; pp. 1209 - 1220
• Main Authors: Zilly, Felipe E, Halemani, Nagaraj D, Walrafen, David, Spitta, Luis, Schreiber, Arne, Jahn, Reinhard, Lang, Thorsten
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 06.04.2011; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Animals; Biological membranes; Ca2; Calcium - metabolism; Calcium channels; Cations; Cations, Divalent - metabolism; Cell Line; Cell Membrane - metabolism; Cluster analysis; Electrostatics; EMBO20; EMBO37; Lipids; Membrane Proteins - metabolism; Membranes; microdomains; Plasma; plasma membrane; Proteins; Rats; signalling; Static Electricity; microdomains; electrostatics; plasma membrane; Ca; signalling
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2011.53

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+ in membrane protein organization. We find that Ca 2+ 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+ influx through voltage‐gated calcium channels and is reversible. In summary, the data demonstrate that the second messenger Ca 2+ strongly influences the organization of membrane proteins, thus adding a novel and unexpected factor that may control the domain structure of biological membranes. This study reveals that calcium influx through voltage‐gated calcium channels triggers reversible redistribution and clustering of plasma membrane proteins.