Disease relevance of Dlg2

• Since platelet-activating factor is a potent neuronal injury mediator during the development of brain trauma, seizures, and ischemia, the present work suggests that PSD-93 might contribute to molecular mechanisms of neuronal damage in these brain disorders [1].

High impact information on Dlg2

• Recombinant PSD-93 was phosphorylated by Fyn in vitro, and Tyr-384 was identified as a major phosphorylation site [2].
• In addition, tyrosine-phosphorylated PSD-93 was able to bind to Csk, a negative regulator of Src family kinases, in vitro as well as in a brain lysate [2].
• Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn [2].
• This suggests that PSD-93 might mediate many NMDA receptor-dependent physiological and pathophysiological functions [1].
• These findings indicate that PSD-93 is involved in the NMDA receptor--nitric oxide-mediated pathological processing of neuronal damage triggered via platelet--activating factor receptor activation [1].

Biological context of Dlg2

• Tyrosine phosphorylation of PSD-93 was greatly reduced in brain tissue from Fyn-deficient mice compared with wild-type mice [2].
• Deletion of PSD-93 alone does not provide neuroprotection after neonatal HI, possibly a result, in part, of upregulation of PSD-95 [3].

Anatomical context of Dlg2

• Chapsyn-110 mRNA was, though at low levels, found over the mantle zone of embryonic brains, and the level was progressively increased in the telencephalon starting at perinatal stages [4].
• Furthermore, mice lacking PSD-93 exhibit blunted NMDAR-dependent persistent pain induced by peripheral nerve injury or injection of Complete Freund's Adjuvant, although they display intact nociceptive responsiveness to acute pain [5].
• To assess the function of this protein complex at neuronal cholinergic synapses in vivo, we examined ganglia in mice that lack PSD93 [6].
• METHODS: Postnatal day 7 wild-type (+/+), heterozygous (+/-), and homozygous (-/-) PSD-93 knockout mice were subjected to HI by permanent ligation of the right carotid artery, followed by exposure to 8% O2/92% N2 for 1 hour [3].

Associations of Dlg2 with chemical compounds

• In addition, the deficiency of PSD-93 markedly attenuated platelet-activating factor-induced increase in cyclic guanosine 3',5'-monophosphate (cGMP) and prevented platelet-activating factor-promoted formation of NMDA receptor-neuronal nitric oxide synthase complex [1].

Co-localisations of Dlg2

• We report here that PSD-93 colocalizes and interacts with the NMDA receptor and neuronal nitric oxide synthase in cultured cortical neurons [1].

Other interactions of Dlg2

• Furthermore, GluRdelta2 and PSD-93 proteins were concentrated at the contacted portion of mismatched synapses, whereas AMPA receptors were distributed in both the contacted and dissociated portions [7].

Analytical, diagnostic and therapeutic context of Dlg2

• After denervation, however, synaptic clusters of nAChRs disassemble much faster in mice lacking PSD93 than those in wild-type mice [6].

References