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 - Funding Information:
Funding and additional information—This work was supported by Startup funds from the Munroe-Meyer Institute and grants from the Alzheimer's association, the Nebraska Research Initiative, an Institutional Development Award (IDeA) under NIGMS, National Institutes of Health, Grant 5P20GM103471-10 (to C. L., E. S., and J. A.), Nebraska EPSCoR Grant EPS-1004094 (to J. A.), RO3 from National Institutes of Health Grant 1R03MH110726-01 (to J. A.), and the Edna Ittner Pediatric Research Fund. L. Y. and E. S. were supported in part by a graduate student fellowship from the University of Nebraska Medical Center. This work was also supported by NIA, National Institutes of Health, Grant AG031158 (to N. W. D., T. R. C., and S. J. B.) and NIMH, National Institutes of Health, Grant MH106425 (to S. J. B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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
VL - 295
SP - 10988
EP - 11001
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 32
ER -