Not all proteins that accumulate in a specific subcellular compartment undergo processes of selective sorting and transport. Some proteins seem to be localized by a mechanism known as selective retention, which describes that cargoes are transported nonselectively to both axons and dendrites, but are eliminated at one side by selective endocytosis and retained at the other, where endocytosis is prevented. Prominent examples for this process are the proteins VAMP2 and NgCAM. NgCAM is sorted into carriers that preferentially deliver their cargo proteins to the axonal membrane. In contrast, VAMP2 is delivered to the surface of both axons and dendrites; however it is preferentially endocytosed from the dendritic membrane, a process, which also results in an axonal enrichment31. Indeed, VAMP2 harbors an endocytosis signal in its cytoplasmic domain, and mutation of this sequence consistently results in an evenly distribution of VAMP2 to cell body, dendrites, and axon. Although such process initially sounds like a waste of cellular energy, some proteins are localized by selective retention, rather than by selective sorting and transport.
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