TY - JOUR
T1 - d-Catenin engages the autophagy pathway to sculpt the developing dendritic arbor
AU - Ligon, Cheryl
AU - Seong, Eunju
AU - Schroeder, Ethan J.
AU - DeKorver, Nicholas W.
AU - Yuan, Li
AU - Chaudoin, Tammy R.
AU - Cai, Yu
AU - Buch, Shilpa
AU - Bonasera, Stephen J.
AU - Arikkath, Jyothi
N1 - Publisher Copyright:
© 2020 Ligon et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2020/8/7
Y1 - 2020/8/7
N2 - The development of the dendritic arbor in pyramidal neurons is critical for neural circuit function. Here, we uncovered a pathway in which d-catenin, a component of the cadherin-catenin cell adhesion complex, promotes coordination of growth among individual dendrites and engages the autophagy mechanism to sculpt the developing dendritic arbor. Using a rat primary neuron model, time-lapse imaging, immunohistochemistry, and confocal microscopy, we found that apical and basolateral dendrites are coordinately sculpted during development. Loss or knockdown of d-catenin uncoupled this coordination, leading to retraction of the apical dendrite without altering basolateral dendrite dynamics. Autophagy is a key cellular pathway that allows degradation of cellular components. We observed that the impairment of the dendritic arbor resulting from d-catenin knockdown could be reversed by knockdown of autophagy-related 7 (ATG7), a component of the autophagy machinery. We propose that d-catenin regulates the dendritic arbor by coordinating the dynamics of individual dendrites and that the autophagy mechanism may be leveraged by d-catenin and other effectors to sculpt the developing dendritic arbor. Our findings have implications for the management of neurological disorders, such as autism and intellectual disability, that are characterized by dendritic aberrations.
AB - The development of the dendritic arbor in pyramidal neurons is critical for neural circuit function. Here, we uncovered a pathway in which d-catenin, a component of the cadherin-catenin cell adhesion complex, promotes coordination of growth among individual dendrites and engages the autophagy mechanism to sculpt the developing dendritic arbor. Using a rat primary neuron model, time-lapse imaging, immunohistochemistry, and confocal microscopy, we found that apical and basolateral dendrites are coordinately sculpted during development. Loss or knockdown of d-catenin uncoupled this coordination, leading to retraction of the apical dendrite without altering basolateral dendrite dynamics. Autophagy is a key cellular pathway that allows degradation of cellular components. We observed that the impairment of the dendritic arbor resulting from d-catenin knockdown could be reversed by knockdown of autophagy-related 7 (ATG7), a component of the autophagy machinery. We propose that d-catenin regulates the dendritic arbor by coordinating the dynamics of individual dendrites and that the autophagy mechanism may be leveraged by d-catenin and other effectors to sculpt the developing dendritic arbor. Our findings have implications for the management of neurological disorders, such as autism and intellectual disability, that are characterized by dendritic aberrations.
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U2 - 10.1074/jbc.ra120.013058
DO - 10.1074/jbc.ra120.013058
M3 - Article
C2 - 32554807
AN - SCOPUS:85089301956
SN - 0021-9258
VL - 295
SP - 10988
EP - 11001
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 32
ER -