Signalling at membrane contact sites: two membranes come together to handle second messengers.

It is now clear that many intracellular signals result from multiple membrane-bound compartments acting in concert. Membrane contact sites, regions of close apposition between organelles, have emerged as major points of convergence during signalling, as these are places where material is exchanged. The material exchanged can be either water-insoluble molecules such as membrane lipids that are passed directly between organelles, or ions such as Ca(2+). Here we highlight new insights into the role of contacts in signalling by second messengers, including lipid traffic that underpins re-generation of IP3, the regulation of NAADP and store-operated Ca(2+) signals, and possible involvement in cyclic AMP signalling.