@misc{oai:ir.soken.ac.jp:00001070,
author = {CHOW, PAKHONG Jeremy and チョウ, パク ホンジェレミー and CHOW, PAKHONG Jeremy},
month = {2016-02-17, 2016-02-17},
note = {Protein tyrosine phosphatase receptor type Z (Ptprz, also known as PTPζ or RPTPβ) is
preferentially expressed in the brain as a major chondroitin sulfate proteoglycan.
Three splicing variants, two receptor-type isoforms and one secretory isoform, are
known. Ptprz interacts with the PSD95 family through its intracellular
carboxyl-terminal PDZ-binding motif in the postsynaptic density of the adult brain.
Ptprz>-deficient mice display impairments in spatial and contextual learning. Here, I
show that the extracellular region of the receptor isoforms of Ptprz are cleaved by
metalloproteinases including ADAM-17 (TACE) and subsequently the
membrane-tethered fragment is cleaved by presenilin/γ-secretase, releasing its
intracellular region into the cytoplasm: Noteworthily, the intracellular fragment of
Ptprz shows nuclear localization. Administration of GM6001, an inhibitor of
metalloproteinases, to mice demonstrated the metalloproteinase-mediated cleavage of
Ptprz under physiological conditions. Furthermore, I identified the cleavage sites in
the extracellular juxtamembrane region of Ptprz by TACE and MMP-9. This is the
first evidence of the metalloproteinase-mediated processing of an RPTP in the central
nervous system.
I also identified the proteolytic processing of Ptprz by plasmin in the adult mouse
brain, which is markedly enhanced after kainate-induced seizures. We estimated the
cleavage sites in the extracellular region of Ptprz based on cell-based assays and in vitrodigestion experiments with recombinant proteins. The findings indicate that Ptprz is a
physiological target for activity-dependent proteolytic processing by the tPA/plasmin
system, and suggest that the proteolytic fragments are involved in the structural and
functional processes of the synapses during learning and memory.
, application/pdf, 総研大甲第1204号},
title = {Proteolytic processing of protein tyrosine phosphatase receptor type Z in the CNS},
year = {}
}