A role for proteolytic regulation of δ-catenin in remodeling a subpopulation of dendritic spines in the rodent brain

摘要

Neural wiring and activity are essential for proper brain function and behavioral outputs and rely on mechanisms that guide the formation, elimination, and remodeling of synapses. During development, it is therefore vital that synaptic densities and architecture are tightly regulated to allow for appropriate neural circuit formation and function. δ-Catenin, a component of the cadherin–catenin cell adhesion complex, has been demonstrated to be a critical regulator of synaptic density and function in the developing central neurons. In this study, we identified forms of δ-catenin that include only the N-terminal (DcatNT) or the C-terminal (DcatCT) regions. We found that these δ-catenin forms are differentially expressed in different regions of the male mouse brain. Our results also indicated that in rat primary cortical culture, these forms are generated in an activity-dependent manner by Ca²⁺-dependent and calpain-mediated cleavage of δ-catenin or in an activity-independent but lysosome-dependent manner. Functionally, loss of the domain containing the calpain-cleavage sites allowing for generation of DcatCT and DcatNT perturbed the density of a subpopulation of dendritic protrusions in rat hippocampal neurons. This subpopulation likely included protrusions that are either in transition toward becoming mature mushroom spines or in the process of being eliminated. By influencing this subpopulation of spines, proteolytic processing of δ-catenin can likely regulate the balance between mature and immature dendritic protrusions in coordination with neural activity. We conclude that by undergoing cleavage, δ-catenin differentially regulates the densities of subpopulations of dendritic spines and contributes to proper neural circuit wiring in the developing brain.