Acidic motif responsible for plasma membrane association of the voltage-dependent calcium channel beta1b subunit.
Voltage-dependent calcium channels consist of a pore-forming transmembrane alpha1-subunit, which is known to associate with a number of accessory subunits, including alpha2-delta- and beta-subunits. The beta-subunits, of which four have been identified (beta1-4), are intracellular proteins that have marked effects on calcium channel trafficking and function. In a previous study, we observed that the beta1b-subunit showed selective plasma membrane association when expressed alone in COS7 cells, whereas beta3 and beta4 did not. In this study, we have examined the basis for this, and have identified, by making chimeric beta-subunits, that the C-terminal region, which shows most diversity between beta-subunits, of beta1b is responsible for its plasma membrane association. Furthermore we have identified, by deletion mutations, an 11-amino acid motif present in the C terminus of beta1b but not in beta3 (amino acids 547-556 of beta1b, WEEEEDYEEE), which when deleted, reduces membrane association of beta1b. Future research aims to identify what is binding to this sequence in beta1b to promote membrane association of this calcium channel subunit. It is possible that such membrane association is important for the selective localization or clustering of particular calcium channels with which beta1b is associated.
Bogdanov
Y
Y
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Brice
N L
NL
Canti
C
C
Page
K M
KM
Li
M
M
Volsen
S G
SG
Dolphin
A C
AC
D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics*; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D002678:Chimera / Q000235:genetics; D002522:Chlorocebus aethiops; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004285:Dogs; D004594:Electrophysiology; D017353:Gene Deletion; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D014162:Transfection / Q000235:genetics; D014981:Xenopus
D015220:Calcium Channels; D004247:DNA