Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro

Dendritic outgrowth and arborization are important for establishing neural circuit formation. To date, little information exists about the involvement of the extracellular matrix (ECM) and its cellular receptors in these processes. In our studies, we focus on the role of dystroglycan (DG), a cell ad...

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Main Authors: Monika eBijata, Jakub eWlodarczyk, Izabela eFigiel
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-05-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00199/full
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author Monika eBijata
Jakub eWlodarczyk
Izabela eFigiel
author_facet Monika eBijata
Jakub eWlodarczyk
Izabela eFigiel
author_sort Monika eBijata
collection DOAJ
description Dendritic outgrowth and arborization are important for establishing neural circuit formation. To date, little information exists about the involvement of the extracellular matrix (ECM) and its cellular receptors in these processes. In our studies, we focus on the role of dystroglycan (DG), a cell adhesion molecule that links ECM components to the actin cytoskeleton, in dendritic development and branching. Using a lentiviral vector (LV) to deliver short-hairpin RNA (shRNA) that specifically silences DG in cultured hippocampal neurons, we found that DG knockdown exerted an inhibitory effect on dendritic tree growth and arborization. The structural changes were associated with activation of the guanosine triphosphatase (GTPase) Cdc42. The overexpression of DG promoted dendritic length and branching. Furthermore, exposure of the cultures to autoactivating matrix metalloproteinase-9 (aaMMP-9), a β-DG-cleaving protease, decreased the complexity of dendritic arbors. This effect was abolished in neurons that overexpressed a β-DG mutant that was defective in MMP-9-mediated cleavage. Altogether, our results indicate that DG controls dendritic arborization in vitro in MMP-9-dependent manner.
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spelling doaj.art-d7c55ea42e8e4bccbb609bc9a21342b82022-12-22T01:38:09ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-05-01910.3389/fncel.2015.00199141893Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitroMonika eBijata0Jakub eWlodarczyk1Izabela eFigiel2Nencki Institute of Experimental BiologyNencki Institute of Experimental BiologyNencki Institute of Experimental BiologyDendritic outgrowth and arborization are important for establishing neural circuit formation. To date, little information exists about the involvement of the extracellular matrix (ECM) and its cellular receptors in these processes. In our studies, we focus on the role of dystroglycan (DG), a cell adhesion molecule that links ECM components to the actin cytoskeleton, in dendritic development and branching. Using a lentiviral vector (LV) to deliver short-hairpin RNA (shRNA) that specifically silences DG in cultured hippocampal neurons, we found that DG knockdown exerted an inhibitory effect on dendritic tree growth and arborization. The structural changes were associated with activation of the guanosine triphosphatase (GTPase) Cdc42. The overexpression of DG promoted dendritic length and branching. Furthermore, exposure of the cultures to autoactivating matrix metalloproteinase-9 (aaMMP-9), a β-DG-cleaving protease, decreased the complexity of dendritic arbors. This effect was abolished in neurons that overexpressed a β-DG mutant that was defective in MMP-9-mediated cleavage. Altogether, our results indicate that DG controls dendritic arborization in vitro in MMP-9-dependent manner.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00199/fullExtracellular MatrixCdc42DystroglycanMMP-9dendritic arborization
spellingShingle Monika eBijata
Jakub eWlodarczyk
Izabela eFigiel
Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
Frontiers in Cellular Neuroscience
Extracellular Matrix
Cdc42
Dystroglycan
MMP-9
dendritic arborization
title Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
title_full Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
title_fullStr Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
title_full_unstemmed Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
title_short Dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
title_sort dystroglycan controls dendritic morphogenesis of hippocampal neurons in vitro
topic Extracellular Matrix
Cdc42
Dystroglycan
MMP-9
dendritic arborization
url http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00199/full
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AT jakubewlodarczyk dystroglycancontrolsdendriticmorphogenesisofhippocampalneuronsinvitro
AT izabelaefigiel dystroglycancontrolsdendriticmorphogenesisofhippocampalneuronsinvitro