title: A proteomic approach to understand MMP-3-driven developmental processes in the postnatal cerebellum: Chaperonin CCT6A and MAP kinase as contributing factors.
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.
authors: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors: Inge
authors: I
authors: Van Hove
authors: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors: Mieke
authors: M
authors: Verslegers
authors: Laboratory of Neuroplasticity and Neuroproteomics, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors: Tjing-Tjing
authors: TT
authors: Hu
authors: School of Biosciences, University of Kent, Canterbury, CT2 7NJ, United Kingdom.
authors: Martin
authors: M
authors: Carden
authors: Laboratory of Neuroplasticity and Neuroproteomics, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors: Lutgarde
authors: L
authors: Arckens
authors: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors: Lieve
authors: L
authors: Moons
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism*; D056404:Chaperonin Containing TCP-1 / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D020935:MAP Kinase Signaling System / Q000502:physiology; D013058:Mass Spectrometry; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D040901:Proteomics
chemical_list: C000607571:CCT6A protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D056404:Chaperonin Containing TCP-1
keywords: MAP kinase; cerebellum; chaperonin containing TCP-1; development; matrix metalloproteinase-3