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Gain control of N ‐methyl‐ D ‐aspartate receptor activity by receptor‐like protein tyrosine phosphatase α
Author(s) -
Lei Gang,
Xue Sheng,
Chéry Nadège,
Liu Qiang,
Xu Jindong,
Kwan Chun L.,
Fu YangPing,
Lu YouMing,
Liu Mingyao,
Harder Kenneth W.,
Yu XianMin
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf292
Subject(s) - biology , protein tyrosine phosphatase , phosphatase , alpha (finance) , receptor , interleukin 5 receptor alpha subunit , biochemistry , protein phosphatase 2 , tyrosine , microbiology and biotechnology , enzyme , g alpha subunit , protein subunit , gene , medicine , construct validity , nursing , patient satisfaction
Src kinase regulation of N ‐methyl‐ D ‐aspartate (NMDA) subtype glutamate receptors in the central nervous system (CNS) has been found to play an important role in processes related to learning and memory, ethanol sensitivity and epilepsy. However, little is known regarding the mechanisms underlying the regulation of Src family kinase activity in the control of NMDA receptors. Here we report that the distal phosphatase domain (D2) of protein tyrosine phosphatase α (PTPα) binds to the PDZ2 domain of post‐synaptic density 95 (PSD95). Thus, Src kinase, its activator (PTPα) and substrate (NMDA receptors) are linked by the same scaffold protein, PSD95. Removal of PTPα does not affect the association of Src with NMDA receptors, but turns off the constitutive regulation of NMDA receptors by the kinase. Further more, we found that application of the PTPα catalytic domains (D1 + D2) into neurones enhances NMDA receptor‐mediated synaptic responses. Conversely, the blockade of endogenous PTPα inhibits NMDA receptor activity and the induction of long‐term potentiation in hippocampal neurones. Thus, PTPα is a novel up‐regulator of synaptic strength in the CNS.