Brice, Nicola Laura; (1998) Voltage dependent calcium channels: Subcellular subunit localisation and targeting. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The voltage dependent calcium channel is a heteromultimer, composing of a pore forming α1 subunit (α1A-E, α1G and α1S) that determines the characteristics of the channel and the accessory subunits α2-δ and β. The aim of this study was to investigate the subcellular localisation of the VDCC subunits, in polarised and non-polarised expression systems and the effect co-expression of different subunit combinations had on the targeting of the complex. I studied the localisation of the subunits in COS-7 cells and found that the α1 subunits A, B and C were localised throughout with the cell if expressed either alone or in combination with α2-δ. However, the αl subunits were targeted to the plasma membrane if co-expressed with any of the β subunits, β1b, β2a, β3b or β4a, or α2-δ/β. Similarly, the α2-δ subunit required the presence of a β subunit for plasma membrane localisation when co-expressed with αlA. The β subunit localisation in COS-7 cells was not affected by the co-expression of the αl/α2-δ. Whether expressed alone or in combination the β1a, βlb and β2a subunits were preferentially targeted to the plasma membrane, whereas the β3b and β4a were localised throughout intracellular regions of the cell. Chimeras, β1b/3b and β3b/1b, in which the C-terminal region of the β1b and β3b subunit were exchanged, showed reversal of localisation patterns of the β subunits, indicating that the C-terminal region is responsible for the plasma membrane localisation of the β1b subunit. When expressed alone in polarised Madin-Darby canine kidney cells (MDCK) the αl subunits were again localised to intracellular regions of the cell, but on co-expression of a β subunit plasma membrane localisation was observed. However, the membrane to which the complex was targeted varied depending on the αl subunit and to a lesser extent the β subunit with which it was co-expressed.

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