The plasma membrane of neurons can be divided into two domains, the soma-dendritic and the axonal. These domains perform different functions: the dendritic surface receives and processes information while the axonal surface is specialized for the rapid transmission of electrical impulses. This functional specialization is generated by sorting and anchoring mechanisms that guarantee the correct delivery and retention of specific membrane proteins. Our understanding of neuronal membrane protein sorting is primarily based on studies of protein overexpression in cultured neurons. These studies revealed that newly synthesized membrane proteins are segregated in the Golgi apparatus in the cell body from where they are transported to the axonal or dendritic surface. Such segregation presumably depends on sorting motifs in the proteins' primary structure. They appear to be located in the cytoplasmic tail for dendritic proteins and in the transmembrane-ectodomain for axonal proteins. Recent studies on neurotransmitter segregation suggest that anchoring in the correct subdomain of the plasma membrane also requires cytoplasmic tail information for binding to the cytoskeleton either directly or by linker proteins. Both mechanisms, sorting and retention, gradually mature during neural development. Young neurons appear to develop initial polarity by other mechanisms, presumably analogous to the mechanisms used by migrating cells. (C) 1998 Elsevier Science B.V. All rights reserved.