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Human neuronal stargazin-like proteins, gamma(2), gamma(3) and gamma(4); an investigation of their specific localization in human brain and their influence on Ca(V)2.1 voltage-dependent calcium channels expressed in Xenopus oocytes

Moss, FJ; Dolphin, AC; Clare, JJ; (2003) Human neuronal stargazin-like proteins, gamma(2), gamma(3) and gamma(4); an investigation of their specific localization in human brain and their influence on Ca(V)2.1 voltage-dependent calcium channels expressed in Xenopus oocytes. BMC NEUROSCI , 4 , Article 23. Green open access

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Abstract

Background: Stargazin (gamma(2)) and the closely related gamma(3), and gamma(4) transmembrane proteins are part of a family of proteins that may act as both neuronal voltage-dependent calcium channel (VDCC) gamma subunits and transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproponinc (AMPA) receptor regulatory proteins (TARPs). In this investigation, we examined the distribution patterns of the stargazin-like proteins gamma(2), gamma(3), and gamma(4) in the human central nervous system (CNS). In addition, we investigated whether human gamma(2) or gamma(4) could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes.Results: The mRNA encoding human gamma(2) is highly expressed in cerebellum, cerebral cortex, hippocampus and thalamus, whereas gamma(3) is abundant in cerebral cortex and amygdala and gamma(4) in the basal ganglia. Immunohistochemical analysis of the cerebellum determined that both gamma(2) and gamma(4) are present in the molecular layer, particularly in Purkinje cell bodies and dendrites, but have an inverse expression pattern to one another in the dentate cerebellar nucleus. They are also detected in the interneurons of the granule cell layer though only gamma(2) is clearly detected in granule cells. The hippocampus stains for gamma(2) and gamma(4) throughout the layers of the every CA region and the dentate gyrus, whilst gamma(3) appears to be localized particularly to the pyramidal and granule cell bodies. When co-expressed in Xenopus oocytes with a Ca(V)2.1/beta(4) VDCC complex, either in the absence or presence of an alpha(2)delta(2) subunit, neither gamma(2) nor gamma(4) significantly modulated the VDCC peak current amplitude, voltage-dependence of activation or voltage-dependence of steady-state inactivation.Conclusion: The human gamma(2), gamma(3) and gamma(4) stargazin-like proteins are detected only in the CNS and display differential distributions among brain regions and several cell types in found in the cerebellum and hippocampus. These distribution patterns closely resemble those reported by other laboratories for the rodent orthologues of each protein. Whilst the fact that neither gamma(2) nor gamma(4) modulated the properties of a VDCC complex with which they could associate in vivo in Purkinje cells adds weight to the hypothesis that the principal role of these proteins is not as auxiliary subunits of VDCCs, it does not exclude the possibility that they play another role in VDCC function.

Type: Article
Title: Human neuronal stargazin-like proteins, gamma(2), gamma(3) and gamma(4); an investigation of their specific localization in human brain and their influence on Ca(V)2.1 voltage-dependent calcium channels expressed in Xenopus oocytes
Open access status: An open access version is available from UCL Discovery
Publisher version: http://www.biomedcentral.com/bmcneurosci/
Keywords: CEREBELLAR GRANULE NEURONS, MATURE RAT-BRAIN, CA2+ CHANNEL, SKELETAL-MUSCLE, BETA-SUBUNITS, ANTIGEN RETRIEVAL, MOUSE STARGAZER, AMPA RECEPTORS, MESSENGER-RNAS, MUTANT MOUSE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/508
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