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Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration

Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule (MT) network. Among various factors that regulate MT dynamics and stability, post-translational modifications (PTMs) of MTs play a critical role in conferring specificity of regulatory protein binding to MTs....

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Autores principales: Liang, Chen, Carrel, Damien, Singh, Nisha K., Hiester, Liam L., Fanget, Isabelle, Kim, Hyuck, Firestein, Bonnie L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755936/
https://www.ncbi.nlm.nih.gov/pubmed/35014548
http://dx.doi.org/10.1177/17590914211062765
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author Liang, Chen
Carrel, Damien
Singh, Nisha K.
Hiester, Liam L.
Fanget, Isabelle
Kim, Hyuck
Firestein, Bonnie L.
author_facet Liang, Chen
Carrel, Damien
Singh, Nisha K.
Hiester, Liam L.
Fanget, Isabelle
Kim, Hyuck
Firestein, Bonnie L.
author_sort Liang, Chen
collection PubMed
description Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule (MT) network. Among various factors that regulate MT dynamics and stability, post-translational modifications (PTMs) of MTs play a critical role in conferring specificity of regulatory protein binding to MTs. Thus, it is important to understand the regulation of PTMs during brain development as multiple developmental processes are dependent on MTs. In this study, we identified that carboxypeptidase E (CPE) changes tubulin polyglutamylation, a major PTM in the brain, and we examine the impact of CPE-mediated changes to polyglutamylation on cortical neuron migration and dendrite morphology. We show, for the first time, that overexpression of CPE increases the level of polyglutamylated α-tubulin while knockdown decreases the level of polyglutamylation. We also demonstrate that CPE-mediated changes to polyglutamylation are dependent on the CPE zinc-binding motif and that this motif is necessary for CPE action on p150(Glued) localization. However, overexpression of a CPE mutant that does not increase MT glutamylation mimics the effects of overexpression of wild type CPE on dendrite branching. Furthermore, although overexpression of wild type CPE does not alter cortical neuron migration, overexpression of the mutant may act in a dominant-negative manner as it decreases the number of neurons that reach the cortical plate (CP), as we previously reported for CPE knockdown. Overall, our data suggest that CPE changes MT glutamylation and redistribution of p150(Glued) and that this function of CPE is independent of its role in shaping dendrite development but plays a partial role in regulating cortical neuron migration.
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spelling pubmed-87559362022-01-14 Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration Liang, Chen Carrel, Damien Singh, Nisha K. Hiester, Liam L. Fanget, Isabelle Kim, Hyuck Firestein, Bonnie L. ASN Neuro Original Papers Neuronal migration and dendritogenesis are dependent on dynamic changes to the microtubule (MT) network. Among various factors that regulate MT dynamics and stability, post-translational modifications (PTMs) of MTs play a critical role in conferring specificity of regulatory protein binding to MTs. Thus, it is important to understand the regulation of PTMs during brain development as multiple developmental processes are dependent on MTs. In this study, we identified that carboxypeptidase E (CPE) changes tubulin polyglutamylation, a major PTM in the brain, and we examine the impact of CPE-mediated changes to polyglutamylation on cortical neuron migration and dendrite morphology. We show, for the first time, that overexpression of CPE increases the level of polyglutamylated α-tubulin while knockdown decreases the level of polyglutamylation. We also demonstrate that CPE-mediated changes to polyglutamylation are dependent on the CPE zinc-binding motif and that this motif is necessary for CPE action on p150(Glued) localization. However, overexpression of a CPE mutant that does not increase MT glutamylation mimics the effects of overexpression of wild type CPE on dendrite branching. Furthermore, although overexpression of wild type CPE does not alter cortical neuron migration, overexpression of the mutant may act in a dominant-negative manner as it decreases the number of neurons that reach the cortical plate (CP), as we previously reported for CPE knockdown. Overall, our data suggest that CPE changes MT glutamylation and redistribution of p150(Glued) and that this function of CPE is independent of its role in shaping dendrite development but plays a partial role in regulating cortical neuron migration. SAGE Publications 2022-01-11 /pmc/articles/PMC8755936/ /pubmed/35014548 http://dx.doi.org/10.1177/17590914211062765 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Papers
Liang, Chen
Carrel, Damien
Singh, Nisha K.
Hiester, Liam L.
Fanget, Isabelle
Kim, Hyuck
Firestein, Bonnie L.
Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration
title Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration
title_full Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration
title_fullStr Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration
title_full_unstemmed Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration
title_short Carboxypeptidase E Independently Changes Microtubule Glutamylation, Dendritic Branching, and Neuronal Migration
title_sort carboxypeptidase e independently changes microtubule glutamylation, dendritic branching, and neuronal migration
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8755936/
https://www.ncbi.nlm.nih.gov/pubmed/35014548
http://dx.doi.org/10.1177/17590914211062765
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