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Membrane-type 5 matrix metalloproteinase is expressed in differentiated neurons and regulates axonal growth
H Hayashita-Kinoh1, H Kinoh, A Okada
1Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Minato-Ku, Tokyo, 108-8639, Japan.
Abstract:
Expression of membrane-type (MT) 5 matrix metalloproteinase (MMP) in the mouse brain was examined. MT5-MMP was expressed in the cerebrum in embryos, but it declined after birth. In contrast, expression in the cerebellum started to increase postnatally and continued thereafter. The cells expressing MT5-MMP were postmitotic neurons that showed gelatinolytic activities. Specific expression of MT5-MMP was observed in the neurons but not in the glial cells when embryonal mouse carcinoma P19 cells were differentiated in vitro by retinoic acid treatment. Neurons isolated from dorsal root ganglia also expressed MT5-MMP, and it was localized at the edge of growth cone. Proteoglycans inhibit neurite extension and regulate synaptogenesis. The inhibitory effect of the proteoglycans on neurite extension of dorsal root ganglia neurons was effectively eliminated by recombinant MT5-MMP. Thus, MT5-MMP expressed in neurons may play a role in axonal growth that contributes to the regulation of neural network formation.
Insights
Membrane-type 5 matrix metalloproteinase (MT5-MMP) expression in the mouse brain changes after birth, with neurons showing gelatinolytic activity. MT5-MMP aids axonal growth by reducing proteoglycan inhibition, regulating neural network formation.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Matrix metalloproteinases (MMPs) are crucial for extracellular matrix remodeling.
- Membrane-type MMPs (MT-MMPs) have specific roles in tissue development and function.
- The function of MT5-MMP in the nervous system is not fully understood.
Purpose of the Study:
- To investigate the expression pattern of MT5-MMP in the developing mouse brain.
- To determine the cellular localization and enzymatic activity of MT5-MMP.
- To explore the role of MT5-MMP in neuronal development and neurite outgrowth.
Main Methods:
- Quantitative analysis of MT5-MMP expression in embryonic and postnatal mouse brains.
- In vitro differentiation of P19 cells and primary neuronal cultures.
- Gelatin zymography to assess enzymatic activity.
- Treatment of dorsal root ganglia neurons with recombinant MT5-MMP.
Main Results:
- MT5-MMP expression is high in the embryonic cerebrum, decreases postnatally, and increases in the cerebellum.
- MT5-MMP is expressed in postmitotic neurons and exhibits gelatinolytic activity.
- MT5-MMP localizes to the growth cone edge in dorsal root ganglia neurons.
- Recombinant MT5-MMP effectively overcomes proteoglycan-mediated inhibition of neurite extension.
Conclusions:
- MT5-MMP expression is developmentally regulated in the mouse brain, with distinct patterns in different regions.
- Neurons are the primary cells expressing MT5-MMP, which possesses gelatinolytic activity.
- MT5-MMP plays a significant role in promoting axonal growth and regulating neural network formation by modulating proteoglycan activity.