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Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post-synaptic sites in rat cerebellum.

Garside, ML; Turner, PR; Austen, B; Strehler, EE; Beesley, PW; Empson, RM (2009) Molecular interactions of the plasma membrane calcium ATPase 2 at pre- and post-synaptic sites in rat cerebellum. Neuroscience, 162 (2). pp. 383-395. ISSN 1873-7544 https://doi.org/10.1016/j.neuroscience.2009.04.059
SGUL Authors: Austen, Brian Maxwell

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Abstract

The plasma membrane calcium extrusion mechanism, PMCA (plasma membrane calcium ATPase) isoform 2 is richly expressed in the brain and particularly the cerebellum. Whilst PMCA2 is known to interact with a variety of proteins to participate in important signalling events [Strehler EE, Filoteo AG, Penniston JT, Caride AJ (2007) Plasma-membrane Ca(2+) pumps: structural diversity as the basis for functional versatility. Biochem Soc Trans 35 (Pt 5):919-922], its molecular interactions in brain synapse tissue are not well understood. An initial proteomics screen and a biochemical fractionation approach identified PMCA2 and potential partners at both pre- and post-synaptic sites in synapse-enriched brain tissue from rat. Reciprocal immunoprecipitation and GST pull-down approaches confirmed that PMCA2 interacts with the post-synaptic proteins PSD95 and the NMDA glutamate receptor subunits NR1 and NR2a, via its C-terminal PDZ (PSD95/Dlg/ZO-1) binding domain. Since PSD95 is a well-known partner for the NMDA receptor this raises the exciting possibility that all three interactions occur within the same post-synaptic signalling complex. At the pre-synapse, where PMCA2 was present in the pre-synapse web, reciprocal immunoprecipitation and GST pull-down approaches identified the pre-synaptic membrane protein syntaxin-1A, a member of the SNARE complex, as a potential partner for PMCA2. Both PSD95-PMCA2 and syntaxin-1A-PMCA2 interactions were also detected in the molecular and granule cell layers of rat cerebellar sagittal slices by immunohistochemistry. These specific molecular interactions at cerebellar synapses may allow PMCA2 to closely control local calcium dynamics as part of pre- and post-synaptic signalling complexes.

Item Type: Article
Additional Information: © 2009. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Animals, Blotting, Western, Cerebellum, Disks Large Homolog 4 Protein, Immunohistochemistry, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Isoenzymes, Membrane Proteins, Plasma Membrane Calcium-Transporting ATPases, Protein Structure, Tertiary, Proteomics, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate, Synapses, Synaptosomes, Syntaxin 1, Cerebellum, Synapses, Synaptosomes, Animals, Rats, Rats, Wistar, Isoenzymes, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Receptors, N-Methyl-D-Aspartate, Blotting, Western, Immunohistochemistry, Immunoprecipitation, Proteomics, Protein Structure, Tertiary, Syntaxin 1, Plasma Membrane Calcium-Transporting ATPases, synapse, NMDA receptor, PSD95, PDZ domain, syntaxin-1A, Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, NEUROSCIENCES, synapse, NMDA receptor, PSD95, PDZ domain, syntaxin-1A, NITRIC-OXIDE SYNTHASE, CA2+-ATPASE ISOFORM 2, PROTEIN-KINASE-C, CA2+ PUMP, NMDA RECEPTORS, GUANYLATE KINASES, SNARE COMPLEXES, PSD-95, TERMINALS, NEURONS, Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, NEUROSCIENCES, synapse, NMDA receptor, PSD95, PDZ domain, syntaxin-1A, NITRIC-OXIDE SYNTHASE, CA2+-ATPASE ISOFORM 2, PROTEIN-KINASE-C, CA2+ PUMP, NMDA RECEPTORS, GUANYLATE KINASES, SNARE COMPLEXES, PSD-95, TERMINALS, NEURONS, Neurology & Neurosurgery, 1109 Neurosciences, 1701 Psychology
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Neuroscience
ISSN: 1873-7544
Language: eng
Dates:
DateEvent
18 August 2009Published
4 May 2009Published Online
24 April 2009Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
R01 NS051769-03NINDS NIH HHSUNSPECIFIED
NS51769NINDS NIH HHSUNSPECIFIED
BBS/0338Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
R01 NS051769NINDS NIH HHSUNSPECIFIED
R01 NS051769-02NINDS NIH HHSUNSPECIFIED
PubMed ID: 19406213
Web of Science ID: WOS:000267787500016
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/109668
Publisher's version: https://doi.org/10.1016/j.neuroscience.2009.04.059

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