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.