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

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. © 2015 Wiley Periodicals, Inc.

Citation

Inge Van Hove, Mieke Verslegers, Tjing-Tjing Hu, Martin Carden, Lutgarde Arckens, Lieve Moons. A proteomic approach to understand MMP-3-driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors. Developmental neurobiology. 2015 Sep;75(9):1033-48

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PMID: 25652596

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