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Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line

Brice, NL; Dolphin, AC; (1999) Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line. J PHYSIOL-LONDON , 515 (3) 685 - 694.

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Abstract

1. Voltage-dependent calcium channels (VDCCs) show a highly non-uniform distribution in many cell types, including neurons and other polarized secretory cells. We have examined whether this can be mimicked in a polarized epithelial cell line (Madin-Darby canine kidney), which has been used extensively to study the targeting of proteins.2. We expressed the VDCC alpha 1A, alpha 1B or alpha 1C subunits either alone or in combination with accessory subunits alpha 2-delta and the different beta subunits, and examined their localization immunocytochemically. An alpha 1 subunit was only targeted to the plasma membrane if co-expressed with the accessory subunits.3. The combination alpha 1C/alpha 2-delta and all beta subunits was always localized predominantly to the basolateral membrane. It has been suggested that this is equivalent to somatodendritic targeting in neurons.4. In contrast, the alpha 1B subunit was expressed at the apical membrane with all the accessory subunit combinations, by 24 h after microinjection. This membrane destination shows some parallels with axonal targeting in neurons.5. The alpha 1A subunit was consistently observed at the apical membrane in the combinations alpha 1A/alpha 2-delta/beta 1b or beta 4. In contrast, when co-expressed with alpha 2-delta/beta 2a, alpha 1A w as clearly targeted to the basolateral membrane.6. In conclusion, the VDCC alpha 1 subunit appears to be the primary determinant for targeting the VDCC complex, but the beta subunit can modify this destination, particularly for alpha 1A.

Type: Article
Title: Differential plasma membrane targeting of voltage-dependent calcium channel subunits expressed in a polarized epithelial cell line
Keywords: CEREBELLAR GRANULE NEURONS, CA2+ CHANNELS, BETA-SUBUNIT, N-TYPE, SUBCELLULAR-DISTRIBUTION, MDCK CELLS, SYNAPTIC TRANSMISSION, HIPPOCAMPAL-NEURONS, GENE-EXPRESSION, PURKINJE-CELLS
UCL classification: 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: http://discovery.ucl.ac.uk/id/eprint/131319
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