Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons

Abstract Caldendrin is a Ca2+ binding protein that interacts with multiple effectors, such as the Cav1 L-type Ca2+ channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of...

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Main Authors: Josue A. Lopez, Annamarie Yamamoto, Joseph T. Vecchi, Jussara Hagen, Kyungmoo Lee, Milan Sonka, Marlan R. Hansen, Amy Lee
Format: Article
Language:English
Published: Nature Portfolio 2023-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-29622-9
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author Josue A. Lopez
Annamarie Yamamoto
Joseph T. Vecchi
Jussara Hagen
Kyungmoo Lee
Milan Sonka
Marlan R. Hansen
Amy Lee
author_facet Josue A. Lopez
Annamarie Yamamoto
Joseph T. Vecchi
Jussara Hagen
Kyungmoo Lee
Milan Sonka
Marlan R. Hansen
Amy Lee
author_sort Josue A. Lopez
collection DOAJ
description Abstract Caldendrin is a Ca2+ binding protein that interacts with multiple effectors, such as the Cav1 L-type Ca2+ channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Cav1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Cav1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Cav1 channels to growth-inhibitory pathways in DRGNs of females but not males.
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spelling doaj.art-21d2febb5c354dc8aa9334ab210b832e2023-03-22T11:16:21ZengNature PortfolioScientific Reports2045-23222023-02-0113111310.1038/s41598-023-29622-9Caldendrin represses neurite regeneration and growth in dorsal root ganglion neuronsJosue A. Lopez0Annamarie Yamamoto1Joseph T. Vecchi2Jussara Hagen3Kyungmoo Lee4Milan Sonka5Marlan R. Hansen6Amy Lee7Department of Neuroscience, University of Texas-AustinDepartment of Neuroscience, University of Texas-AustinDepartment of Molecular Physiology and Biophysics and Otolaryngology Head-Neck Surgery, Iowa Neuroscience Institute, Pappajohn Biomedical Institute, University of IowaDepartment of Molecular Physiology and Biophysics and Otolaryngology Head-Neck Surgery, Iowa Neuroscience Institute, Pappajohn Biomedical Institute, University of IowaElectrical and Computer Engineering, Iowa Institute for Biomedical Imaging, University of IowaElectrical and Computer Engineering, Iowa Institute for Biomedical Imaging, University of IowaDepartment of Molecular Physiology and Biophysics and Otolaryngology Head-Neck Surgery, Iowa Neuroscience Institute, Pappajohn Biomedical Institute, University of IowaDepartment of Neuroscience, University of Texas-AustinAbstract Caldendrin is a Ca2+ binding protein that interacts with multiple effectors, such as the Cav1 L-type Ca2+ channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Cav1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Cav1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Cav1 channels to growth-inhibitory pathways in DRGNs of females but not males.https://doi.org/10.1038/s41598-023-29622-9
spellingShingle Josue A. Lopez
Annamarie Yamamoto
Joseph T. Vecchi
Jussara Hagen
Kyungmoo Lee
Milan Sonka
Marlan R. Hansen
Amy Lee
Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
Scientific Reports
title Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
title_full Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
title_fullStr Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
title_full_unstemmed Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
title_short Caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
title_sort caldendrin represses neurite regeneration and growth in dorsal root ganglion neurons
url https://doi.org/10.1038/s41598-023-29622-9
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