Molecular remodeling mechanisms of the neural somatodendritic compartment.

Neuronal cells use the process of vesicle trafficking to manipulate the populations of neurotransmitter receptors and other membrane proteins. Long term potentiation (LTP) is a long-lived increase in synaptic strength between neurons and increases postsynaptic dendritic spine size and the concentration of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor (AMPAR) located in the postsynaptic density. AMPAR is removed from the cell surface via clathrin-mediated endocytosis. While the adaptor protein 2 (AP2) complex of endocytosis seems to have the components needed to allow temporal and spatial regulations of internalization, many accessory proteins are involved, such as epidermal growth factor receptor phosphorylation substrate 15 (Eps15). A sequence of repeats in the Eps15 protein is known as the Eps15 homology (EH) domain. It has affinity for asparagine-proline-phenylalanine (NPF) sequences that are contained within vesicle trafficking proteins such as epsin, Rab11 family interacting protein 2 (Rab11-FIP2), and Numb. After endocytosis, a pool of AMPAR is stored in the endosomal recycling compartment that can be transported to the dendritic spine surface upon stimulation during LTP for lateral diffusion into the postsynaptic density. Rab11 and the Eps15 homologue EHD1 are involved in receptor recycling. EHD family members are also involved in transcytosis of the neuronal cell adhesion molecule neuron-glia cell adhesion molecule (NgCAM) from the somatodendritic compartment to the axon. Neurons have a unique morphology comprising many projections of membrane that is constructed in part by the effects of the Eps15 homologue, intersectin. Morphogenesis in the somatodendritic compartment is becoming better understood, but there is still much exciting territory to explore, especially regarding the roles of various EH domain-NPF interactions in endocytic and recycling processes.
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