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Endocytosis is a fundamental mechanism by which neurons control intercellular signaling, nutrient uptake, and synaptic transmission. This process is carried out by the assembly of clathrin coats and the budding of clathrin-coated vesicles from the neuronal plasma membrane. Here, we demonstrate that in young neurons, clathrin assembly and disassembly occur rapidly, locally, and repeatedly at "hot spots" throughout dendrites and at the tips of dendritic filopodia. In contrast, clathrin coats in mature dendrites reside in stable, long-lasting zones at sites of endocytosis, where clathrin undergoes continuous exchange with local cytosolic pools. In dendritic spines, endocytic zones lie lateral to the postsynaptic density (PSD) where they develop and persist independent of synaptic activity, akin to the PSD itself. These results reveal the presence of a novel specialization dedicated to endocytosis near the postsynaptic membrane.

In the course of studying proteins involved in long-term facilitation in Aplysia, we found that 5-HT and cAMP, a second messenger activated by 5-HT, lead to the removal of a set of N-CAM-related cell adhesion molecules (apCAMs) from the surface membrane of sensory neurons by means of receptor-mediated endocytosis. Here we describe that, as part of this coordinated program for endocytosis, 5-HT and cAMP also induce in the sensory neurons an increase in the density of coated pits and coated vesicles and an increase in the expression of the light chain of Aplysia clathrin (apClathrin). The clathrin-related endocytosis seems designed to internalize and redistribute apCAMs and other surface membrane proteins in the sensory neurons, and thus it appears to constitute one of the initial steps in the growth of new synaptic connections that accompanies long-term facilitation.