title: Dynamic association of calcium channel subunits at the cellular membrane.
abstract: High voltage gated calcium channels (VGCCs) are composed of at least three subunits, one pore forming [Formula: see text]-subunit, an intracellular [Formula: see text]-variant, and a mostly extracellular [Formula: see text]-variant. Interactions between these subunits determine the kinetic properties of VGCCs. It is unclear whether these interactions are stable over time or rather transient. Here, we used single-molecule tracking to investigate the surface diffusion of [Formula: see text]- and [Formula: see text]-subunits at the cell surface. We found that [Formula: see text]-subunits show higher surface mobility than [Formula: see text]-subunits, and that they are only transiently confined together, suggesting a weak association between [Formula: see text]- and [Formula: see text]-subunits. Moreover, we observed that different [Formula: see text]-subunits engage in different degrees of association with the [Formula: see text]-subunit, revealing the tighter interaction of [Formula: see text] with [Formula: see text]. These data indicate a distinct regulation of the [Formula: see text] interaction in VGCC subtypes. We modeled their membrane dynamics in a Monte Carlo simulation using experimentally determined diffusion constants. Our modeling predicts that the ratio of associated [Formula: see text]- and [Formula: see text]-subunits mainly depends on their expression density and confinement in the membrane. Based on the different motilities of particular [Formula: see text]-subunit combinations, we propose that their dynamic assembly and disassembly represent an important mechanism to regulate the signaling properties of VGCC.
authors.affiliation: Otto-von-Guericke-University of Magdeburg , Lehrstuhl Systemverfahrenstechnik, Universitätsplatz 2, Magdeburg D-39106, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Voigt
authors.affiliation: Leibniz-Institute of Neurobiology , Research Group Molecular Physiology, Brenneckestrasse 6, Magdeburg D-39118, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Freund
authors.affiliation: Leibniz-Institute of Neurobiology , Research Group Molecular Physiology, Brenneckestrasse 6, Magdeburg D-39118, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Heck
authors.affiliation: Westfälische Wilhelms-University , Institute of Anatomy and Molecular Neurobiology, Vesaliusweg 2, Münster 48149, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Missler
authors.affiliation: Medical University Innsbruck , Division of Physiology, Department of Physiology and Medical Physics, Schöpfstrasse 41, Innsbruck 6020, Austria.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.affiliation: Leibniz-Institute of Neurobiology , Department Neurochemistry, Brenneckestrasse 6, Magdeburg D-39118, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thomas
authors.affiliation: Leibniz-Institute of Neurobiology, Research Group Molecular Physiology, Brenneckestrasse 6, Magdeburg D-39118, Germany; Otto-von-Guericke-University Magdeburg, Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, Magdeburg D-39106, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heine
keywords: calcium channel; single-particle tracking; surface mobility