NEUROTRYPSIN, A NOVEL MULTIDOMAIN SERINE-PROTEASE EXPRESSED IN THE NERVOUS-SYSTEM

We have cloned a novel murine cDNA encoding a multidomain serine prote ase, termed neurotrypsin, which exhibits an unprecedented domain compo sition. The deduced amino acid sequence defines a mosaic protein of 76 1 amino acids consisting of a kringle domain, followed by three scaven ger receptor cysteine-rich repeats, and a serine protease domain. Base d on comparisons of the primary structure, the protease domain belongs to the subfamily of trypsin-like serine proteases. In situ hybridizat ion revealed that the expression of neurotrypsin in the adult murine n ervous system is confined to distinct subsets of neurons. The most pro minent expression was found in the cerebral cortex, the hippocampus, a nd the amygdala, i.e., structures engaged in the processing and storag e of learned behaviors and memories. Together with the recently obtain ed evidence that extracellular serine proteases play a role in neural plasticity, this expression pattern suggests that the extracellular pr oteolytic action of neurotrypsin subserves structural reorganizations associated with learning and memory operations.