title: Extracellular neurosin degrades α-synuclein in cultured cells.
abstract: Neurosin, also called kallikrein 6, is a trypsin-like serine protease predominantly expressed in the central nervous system. Neurosin may degrade alpha-synuclein, a major component of the Lewy bodies commonly observed in dopaminergic neurons of patients with sporadic Parkinson's disease. In the present study, we investigated the localization and proteolytic activity of human neurosin using cultured cells to elucidate the physiological role of this enzyme at the cellular level. Heterologous expression of pre-pro-neurosin was localized to the endoplasmic reticulum and secreted. The proteolytic activity of neurosin was analyzed by zymography and fluorescent substrate, and showed that extracellular neurosin had protease activity but intracellular neurosin did not. We also coexpressed alpha-synuclein with neurosin and demonstrated that alpha-synuclein was not cleaved within cells, but extracellular alpha-synuclein was degraded by secreted neurosin. These findings suggest that neurosin targets the extracellular alpha-synuclein.
authors.affiliation: Department of Neurology, Research Institute for Neurological Diseases and Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Harutsugu
authors.initials: H
authors.lastname: Tatebe
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Kasai
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
mesh_terms: D004298:Dopamine / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D045604:Extracellular Fluid / Q000201:enzymology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007610:Kallikreins / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D013378:Substantia Nigra / Q000201:enzymology / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D010447:Peptide Hydrolases; C103551:KLK6 protein, human; D007610:Kallikreins; D004298:Dopamine