Coordinated Spine Pruning and Maturation Mediated by Inter-Spine Competition for Cadherin/Catenin Complexes

Abstract

Dendritic spines are postsynaptic compartments of excitatory synapses that undergo dynamic changes during development, including rapid spinogenesis in early postnatal life and significant pruning during adolescence. Spine pruning defects have been implicated in developmental neurological disorders such as autism, yet much remains to be uncovered regarding its molecular mechanism. Here, we show that spine pruning and maturation in the mouse somatosensory cortex are coordinated via the cadherin/catenin cell adhesion complex and bidrectionally regulated by sensory experience. We further demonstrate that locally enhancing cadherin/catenin-dependent adhesion or photo-stimulating a contacting channelrhodopsin-expressing axon stabilized the manipulated spine and eliminated its neighbors, an effect requiring cadherin/catenin-dependent adhesion. Importantly, we show that differential cadherin/catenin-dependent adhesion between neighboring spines biased spine fate in vivo. These results suggest that activity-induced inter-spine competition for β-catenin provides specificity for concurrent spine maturation and elimination and thus is critical for the molecular control of spine pruning during neural circuit refinement.

Spine maturation and pruning during development: Cadherin/Catenin complexes come to help

“…In a recent research article published in Cell, the research group led by Dr. Xiang Yu from the Institute of Neuroscience, Chinese Academy of Sciences, discovered that the Cadherin/Catenin cell adhesion complex plays a central role in coordinating dendritic spine pruning and maturation during experience-dependent plasticity in vivo [1]. This work significantly extends our current knowledge of the molecular mechanism underlying structural synaptic plasticity.…”

Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects

“…CTNNB1 interacts with α-catenin and N-cadherin to form cell adhesion complex localized at cell membrane and in synaptic junctions (21,70). It controls the synaptic strength and modulates neuronal plasticity in excitatory neurons (15,16,18,20). CTNNB1 may also regulate the electrophysiology of interneurons.…”

“…By interacting with N-cadherin, CTNNB1 shapes synaptic structure (15,16) and regulates excitatory postsynaptic strength (17,18). In addition, the axonal localization and translation of CTNNB1 modulate presynaptic vesicle release (19–21).…”

Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops

“…5B2). For clarity, this model focuses on simple aspects of multiple mutually inhibitory interactions between the FMRP and TSC1/2 pathways (Ashley and Warren, 1995; Bian et al, 2015; Darnell and Klann, 2013). …”