Regulation of neuronal function by protein trafficking: a role for the endosomal pathway

Abstract

Protein trafficking plays a central role in many aspects of neuronal function, from the release of neurotransmitters by exocytosis and the recycling of synaptic vesicle proteins to the regulation of receptor signalling. Synaptic function can be significantly modified on a short time scale by alterations in the levels of receptors, ion channels and transporters both preand postsynaptically. In many cases, these alterations appear to be mediated by acute changes in the rates at which the proteins are endocytosed from and exocytosed to the cell surface from intracellular pools. While our current understanding of the signalling mechanisms and the intracellular pathways responsible for these acute changes is still in its infancy, intriguing details are beginning to emerge from a number of systems.

The distribution of neuron-specific gene family member 1 in brain and germ cells: Implications for the regulation of germ-line development by brain

“…Furin is another cytosolic protein, functionally similar to clathrin. CK2 phosphorylation mediates furin association with clathrin adaptors (Buckley et al, 2000). We found two AP motifs and seven CK2 sites in cNSG1, which suggests that cNSG1 interacts significantly with clathrin and furin.…”

“…The primary sequence of cNSG1 consists of several phosphorylation sites of CK2, PKC, N-glycosylation, N-myristoylation, and AP recognition motifs, which play critical roles during endocytosis. For example, protein trafficking through endocytosis achieves steady-state distributions by the recognition of a variety of targeting signals (Buckley et al, 2000). Cytosolic protein clathrin-coated vesicles (CCVs) are responsible for trafficking proteins from the plasma membrane or trans-Golgi network to early endosomes (Kirchhausen, 1999).…”

Mammalian Ykt6 Is a Neuronal SNARE Targeted to a Specialized Compartment by its Profilin-like Amino Terminal Domain

“…Currently, we can only speculate that neurons, because of their remarkably complex pathways of regulated secretion and the membrane remodeling involved in axon and synapse formation and regulation, might have a need for a specialized lysosome-related or dense core granule-related intracellular compartment regulated by ykt6. Presynaptic as well as postsynaptic membranes must undergo cycles of internalization and recycling or degradation (Buckley et al, 2000). In addition, there may be brain-specific protein and lipid degradative pathways.…”

A Conserved Mechanism of Synaptogyrin Localization

“…preSVs might fuse with an endosomal compartment and SVs generated by budding from the endosome. A second, but not mutually exclusive possibility, is that preSVs are delivered to the presynaptic plasma membrane at the nerve terminal and then retrieved by the same mechanism(s) used to recycle SVs after regulated exocytosis (Hannah et al, 1999; reviewed by Buckley et al, 2000). Regardless of the exact route of trafficking to the mature organelle, SV proteins must be sorted away from other membrane proteins at several stages during their life cycle.…”