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A proteomic approach to understand MMP?3?driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors

Van Hove, Ingrid, Verslegers, Mieke, Hu, Tjing-Tjing, Carden, Martin J., Arckens, Lutgarde, Moons, Lieve (2015) A proteomic approach to understand MMP?3?driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors. Developmental Neurobiology, 75 (9). pp. 1033-1048. ISSN 1932-8451. E-ISSN 1932-846X. (doi:10.1002/dneu.22272)

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Abstract

Matrix metalloproteinase?3 (MMP?3) deficiency in mice was previously reported to result in a transiently retarded granule cell migration at postnatal day 8 (P8) and a sustained disturbed arborization of Purkinje cell dendrites from P8 on, concomitant with a delayed synapse formation between granule cells and Purkinje cells and resulting in mild deficits in motor performance in adult animals. However, the molecular mechanisms by which MMP?3 contributes to proper development of the cerebellar cortex during the first postnatal weeks remains unknown. In this study, we used a functional proteomics approach to investigate alterations in protein expression in postnatal cerebella of wild?type versus MMP?3 deficient mice, and to further elucidate MMP?3?dependent pathways and downstream targets in vivo. At P8, two?dimensional difference gel electrophoresis and mass spectrometry identified 20 unique proteins with a different expression between the two genotypes. Subsequent “Ingenuity Pathway Analysis” and Western blotting indicate that the chaperonin containing T?complex polypeptide 1, subunit 6A and the MAP kinase signaling pathway play a key role in the MMP?3?dependent regulation of neurite outgrowth and neuronal migration in the developing brain.

Item Type: Article
DOI/Identification number: 10.1002/dneu.22272
Uncontrolled keywords: cerebellum; development; matrix metalloproteinase-3; chaperonin containing TCP-1; MAP kinase
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculties > Sciences > School of Biosciences
Faculties > Sciences > School of Biosciences > Cell & Developmental Biology Group
Depositing User: Martin Carden
Date Deposited: 28 Oct 2018 18:53 UTC
Last Modified: 29 May 2019 21:22 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/69829 (The current URI for this page, for reference purposes)
Carden, Martin J.: https://orcid.org/0000-0002-0609-4605
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