SPAL, a Rap-specific GTPase activating protein, is present in the NMDA receptor-PSD-95 complex in the hippocampus.
BACKGROUND
The PSD-95 family of proteins possesses multiple protein binding domains, including three PDZ domains, an SH3 domain, a HOOK domain and a guanylate kinase-like (GK) domain. The PSD-95 proteins function as scaffolding proteins that link ion channels such as the N-methyl-d-aspartate-receptors (NMDA-Rs) with cytoskeletal networks and signalling molecules, thereby controlling synaptic plasticity and learning.


RESULTS
We found that the PSD-95 family proteins interact via their GK domains with SPA-1-like protein (SPAL), a GTPase-activating protein (GAP) that is specific for Rap1. SPAL was contained within the NMDA-R-PSD-95 complex, and co-localized with PSD-95 and NMDA-R at the synapses in cultured hippocampal neurones. Furthermore, NMDA stimulation induced the dephosphorylation of SPAL in cultured hippocampal neurones.


CONCLUSIONS
Our findings suggest that SPAL may be involved in the NMDA-mediated organization of cytoskeletal networks and signal transduction.
Roy
Badal C
BC
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.
Kohu
Kazuyoshi
K
Matsuura
Ken
K
Yanai
Hiroyuki
H
Akiyama
Tetsu
T
D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons; D011233:Precipitin Tests; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D020827:rap1 GTP-Binding Proteins