Membrane traffic: Cycling lipids

One of the more fascinating problems in biology is to understand the nerve signalling that enables us to think and feel. The transmission of nerve impulses across synapses is accomplished by the release of signalling molecules, known as neurotransmitters, at nerve terminals. Neurotransmitters are stored in synaptic vesicles and, after the nerve has received the appropriate stimulus, they are released by a Ca2+-stimulated fusion of the vesicles with the presynaptic plasma membrane of the nerve cell. The membrane of a synaptic vesicle is composed of a lipid bilayer with a variety of proteins incorporated [1]. These proteins have diverse functions, such as loading the vesicle with neurotransmitter, targeting the vesicle to nerve terminals, and facilitating the fusion of the vesicle with the plasma membrane. The membrane constituents of synaptic vesicles need to be reused, or ‘recycled’, both in order to maintain membrane homeostasis and because the availability of newly synthesised proteins in the nerve terminal is restricted. Therefore, nerve terminals specialise not only in synaptic vesicle exocytosis, but also in endocytosis — the internalisation of selected domains of the plasma membrane. Endocytosis at the nerve terminal is coupled to exocytosis, so obviously these processes have to be tightly regulated and coordinated. It has recently become clear that phosphoinositides, which are phosphorylated derivatives of the membrane lipid phosphatidylinositol, play a crucial role in this context, and a recent paper by Cremona et al. [2] highlights their importance.