Compartmentalizing the neuronal plasma membrane from axon initial segments to synapses.

Many membrane proteins localize to restricted domains in neurons, such as axons, dendrites, synapses, or axon initial segments. The exquisite subcellular compartmentalization of adhesion molecules, growth factor receptors, signaling receptors, voltage-gated and ligand-gated channels, and others underlies the complex functioning of neurons and ultimately vectorial propagation of signaling in neuronal circuits. This chapter discusses the cellular mechanisms for compartmentalizing the neuronal plasma membrane. Among the mechanisms contributing to protein segregation in the membrane are sorting and targeting in the Golgi/TGN, endocytosis, recycling, and degradation, and control of membrane protein diffusion. The molecular underpinnings of these cellular mechanisms are reviewed in the first part. The second part discusses the contribution of each cellular mechanism to targeting proteins to axons and dendrites, to synapses, to axon initial segments, and to Nodes of Ranvier. For most, if not all proteins and locations, all four mechanisms are in effect and additively contribute to the precise localization of membrane proteins in neurons. Since disruption of proper protein distribution results in defects in neuronal function and can lead to neurodegenerative diseases, a full understanding of the cellular mechanisms of plasma membrane compartmentalization is an important goal for the future.