Neurotrypsin, a novel multidomain serine protease expressed in the nervous system

We have cloned a novel murine cDNA encoding a multidomain serine protease, termed neurotrypsin, which exhibits an unprecedented domain composition. The deduced amino acid sequence defines a mosaic protein of 761 amino acids consisting of a kringle domain, followed by three scavenger receptor cysteine-rich repeats, and a serine protease domain. Based on comparisons of the primary structure, the protease domain belongs to the subfamily of trypsin-like serine proteases. In situ hybridization revealed that the expression of neurotrypsin in the adult murine nervous system is confined to distinct subsets of neurons. The most prominent expression was found in the cerebral cortex, the hippocampus, and the amygdala, i.e., structures engaged in the processing and storage of learned behaviors and memories. Together with the recently obtained evidence that extracellular serine proteases play a role in neural plasticity, this expression pattern suggests that the extracellular proteolytic action of neurotrypsin subserves structural reorganizations associated with learning and memory operations.