Enzymatic properties and localization of motopsin (PRSS12), a protease whose absence causes mental retardation

被引:23
作者
Mitsui, Shinichi [1 ]
Yamaguchi, Nozomi
Osako, Yoji
Yuri, Kazunari
机构
[1] Kochi Med Sci, Dept Neurobiol & Anat, Nankoku, Kochi 7838505, Japan
[2] Kyoto Prefectural Univ Med, Res Inst Geriatr, Dept Cell Biol, Kyoto 6028566, Japan
关键词
serine protease; cerebral cortex; tissue plasminogen activator; neurotrypsin;
D O I
10.1016/j.brainres.2006.11.094
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Motopsin (PRSS12) is a mosaic protease expressed in the central nervous system. Truncation of the human motopsin gene causes nonsyndromic mental retardation. Understanding the enzymatic properties and localization of motopsin protein in the central nervous system will help identify the molecular mechanism by which the loss of motopsin function causes mental retardation. Recombinant motopsin showed amidolytic activity against the synthetic substrate benzyloxycarbonyl-L-phenylalanyl-L-arginine 4-methyl-coumaryl-7-amide. Motopsin activated the single-chain tissue plasminogen activator precursor and exhibited gelatinolytic activity. This enzymatic activity was inhibited by typical serine protease inhibitors such as aprotinin, leupeptin, and (4-amidinophenyl) methanesulfonyl fluoride. Immunocytochemistry using anti-motopsin IgG revealed that both human and mouse motopsin proteins were distributed in discrete puncta along the dendrites and soma as well as axons in cultured hippocampal neurons. In the limbic system, including the cingulate and hippocampal pyramidal neurons and piriform cortex, high level of motopsin protein was expressed at postnatal day 10, but a very low level at 10-week-old mice. Motopsin and tissue plasminogen activator were co-expressed in the cingulate pyramidal neurons at postnatal day 10 and were distributed along dendrites of cultured pyramidal neurons. In cranial nuclei, a moderate level of motopsin protein was detected independently on the developmental stage. Our results suggest that motopsin has multiple functions, such as axon outgrowth, arranging perineuronal environment, and maintaining neuronal plasticity, partly in coordination with other proteases including tissue plasminogen activator. (c) 2006 Elsevier B.V. All rights reserved.
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页码:1 / 12
页数:12
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