Lateral mobility and anchoring of recombinant GABA A receptors depend on subunit composition

Peran, Macarena, Hicks, Barry, Peterson, Nancy, Hooper, Helen and Salas, Ramiro (2001) Lateral mobility and anchoring of recombinant GABA A receptors depend on subunit composition. Cell Motility and the Cytoskeleton, 50 (2). pp. 89-100. ISSN 0886 1544

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Abstract

The clustering of type A γ-aminobutyric acid receptors (GABA AR) at discrete and functionally significant domains on the nerve cell surface is an important determinant in the integration of synaptic inputs. To discern the role that the subunits of the GABA AR play in determining the receptor' s cell surface topography and mobility, the α1, β1, β3, and γ2s subunits were transfected into COS7, HEK293, and PC12 cells and the distribution and cell surface mobility of these recombinant receptors were examined. Our results show that α1 subunits are retained in the endoplasmic reticulum while β1 and β3 subunits are sorted to the plasma membrane where they form clusters. Co-expression and co-assembly of α1 and β3 subunits result in the rescue of intracelular α1 subunits, which are transported as αβ subunit complexes to the cell surface where they formed clusters. Fluorescence photobleach recovery and single particle tracking of recombinant receptors show that, despite clustering, β3 subunit homooligomers are mobile within a cell surface domain. Inclusion of α1 in β3 or β3γ2s complexes, however, dramatically reduces the receptor's lateral mobility in COS 7 and PC12 cells and anchors GABA ARs on the cell surface, suggesting the formation of a direct link to a component of the cytoskeleton. The mobility of recombinant receptors that include the α1 subunit mirrors the mobility of GABA ARs on cell bodies and dendrites of cortical and spinal cord neurons. The results suggest that incorporation of α1 subunits give rise to a population of GABA ARs that are immobilized on the cell surface.

Item Type:	Article
Uncontrolled Keywords:	Anchoring, cytoskeleton, fluorescence photobleach recovery, receptor mobility, single particle tracking
Subjects:	B100 Anatomy, Physiology and Pathology
Department:	Faculties > Health and Life Sciences > Applied Sciences
Depositing User:	Becky Skoyles
Date Deposited:	13 Feb 2015 11:52
Last Modified:	12 Oct 2019 17:29
URI:	http://nrl.northumbria.ac.uk/id/eprint/19258

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