Role of the C terminus of the alpha 1C (CaV1.2) subunit in membrane
targeting of cardiac L-type calcium channels
T. Gao, M. Bunemann, B. Gerhardstein, H. Ma, und M. Hosey. J Biol Chem, 275 (33):
25436-44(August 2000)Gao, T Bunemann, M Gerhardstein, B L Ma, H Hosey, M M HL 23306/HL/NHLBI
NIH HHS/United States Research Support, Non-U.S. Gov't Research Support,
U.S. Gov't, P.H.S. United states The Journal of biological chemistry
J Biol Chem. 2000 Aug 18;275(33):25436-44..
Zusammenfassung
We have previously demonstrated that formation of a complex between
L-type calcium (Ca(2+)) channel alpha(1C) (Ca(V)1.2) and beta subunits
was necessary to target the channels to the plasma membrane when
expressed in tsA201 cells. In the present study, we identified a
region in the C terminus of the alpha(1C) subunit that was required
for membrane targeting. Using a series of C-terminal deletion mutants
of the alpha(1C) subunit, a domain consisting of amino acid residues
1623-1666 ("targeting domain") in the C terminus of the alpha(1C)
subunit has been identified to be important for correct targeting
of L-type Ca(2+) channel complexes to the plasma membrane. Although
cells expressing the wild-type alpha(1C) and beta(2a) subunits exhibited
punctate clusters of channel complexes along the plasma membrane
with little intracellular staining, co-expression of deletion mutants
of the alpha(1C) subunit that lack the targeting domain with the
beta(2a) subunit resulted in an intracellular localization of the
channels. In addition, three other regions in the C terminus of the
alpha(1C) subunit that were downstream of residues 1623-1666 were
found to contribute to membrane targeting of the L-type channels.
Deletion of these domains in the alpha(1C) subunit resulted in a
reduction of plasma membrane-localized channels, and a concomitant
increase in channels localized intracellularly. Taken together, these
results have demonstrated that a targeting domain in the C terminus
of the alpha(1C) subunit was required for proper plasma membrane
localization of the L-type Ca(2+) channels.
Gao, T Bunemann, M Gerhardstein, B L Ma, H Hosey, M M HL 23306/HL/NHLBI
NIH HHS/United States Research Support, Non-U.S. Gov't Research Support,
U.S. Gov't, P.H.S. United states The Journal of biological chemistry
J Biol Chem. 2000 Aug 18;275(33):25436-44.
%0 Journal Article
%1 Gao2000
%A Gao, T.
%A Bunemann, M.
%A Gerhardstein, B. L.
%A Ma, H.
%A Hosey, M. M.
%D 2000
%J J Biol Chem
%K Antibody Binding Calcium Cell Channels, Deletion Fluorescent Gene Humans Immunoblotting L-Type/*chemistry/metabolism/physiology Ligands Line Membrane/metabolism Mutagenesis, Patch-Clamp Precipitin Proline/chemistry Protein Site-Directed Structure, Technique Techniques Tertiary Tests Transfection
%N 33
%P 25436-44
%T Role of the C terminus of the alpha 1C (CaV1.2) subunit in membrane
targeting of cardiac L-type calcium channels
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10816591
%V 275
%X We have previously demonstrated that formation of a complex between
L-type calcium (Ca(2+)) channel alpha(1C) (Ca(V)1.2) and beta subunits
was necessary to target the channels to the plasma membrane when
expressed in tsA201 cells. In the present study, we identified a
region in the C terminus of the alpha(1C) subunit that was required
for membrane targeting. Using a series of C-terminal deletion mutants
of the alpha(1C) subunit, a domain consisting of amino acid residues
1623-1666 ("targeting domain") in the C terminus of the alpha(1C)
subunit has been identified to be important for correct targeting
of L-type Ca(2+) channel complexes to the plasma membrane. Although
cells expressing the wild-type alpha(1C) and beta(2a) subunits exhibited
punctate clusters of channel complexes along the plasma membrane
with little intracellular staining, co-expression of deletion mutants
of the alpha(1C) subunit that lack the targeting domain with the
beta(2a) subunit resulted in an intracellular localization of the
channels. In addition, three other regions in the C terminus of the
alpha(1C) subunit that were downstream of residues 1623-1666 were
found to contribute to membrane targeting of the L-type channels.
Deletion of these domains in the alpha(1C) subunit resulted in a
reduction of plasma membrane-localized channels, and a concomitant
increase in channels localized intracellularly. Taken together, these
results have demonstrated that a targeting domain in the C terminus
of the alpha(1C) subunit was required for proper plasma membrane
localization of the L-type Ca(2+) channels.
@article{Gao2000,
abstract = {We have previously demonstrated that formation of a complex between
L-type calcium (Ca(2+)) channel alpha(1C) (Ca(V)1.2) and beta subunits
was necessary to target the channels to the plasma membrane when
expressed in tsA201 cells. In the present study, we identified a
region in the C terminus of the alpha(1C) subunit that was required
for membrane targeting. Using a series of C-terminal deletion mutants
of the alpha(1C) subunit, a domain consisting of amino acid residues
1623-1666 ("targeting domain") in the C terminus of the alpha(1C)
subunit has been identified to be important for correct targeting
of L-type Ca(2+) channel complexes to the plasma membrane. Although
cells expressing the wild-type alpha(1C) and beta(2a) subunits exhibited
punctate clusters of channel complexes along the plasma membrane
with little intracellular staining, co-expression of deletion mutants
of the alpha(1C) subunit that lack the targeting domain with the
beta(2a) subunit resulted in an intracellular localization of the
channels. In addition, three other regions in the C terminus of the
alpha(1C) subunit that were downstream of residues 1623-1666 were
found to contribute to membrane targeting of the L-type channels.
Deletion of these domains in the alpha(1C) subunit resulted in a
reduction of plasma membrane-localized channels, and a concomitant
increase in channels localized intracellularly. Taken together, these
results have demonstrated that a targeting domain in the C terminus
of the alpha(1C) subunit was required for proper plasma membrane
localization of the L-type Ca(2+) channels.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Gao, T. and Bunemann, M. and Gerhardstein, B. L. and Ma, H. and Hosey, M. M.},
biburl = {https://www.bibsonomy.org/bibtex/2d5a2e0e8a77033834b1215019406a904/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {45cf656b86e226f5b83efb8d633c5adb},
intrahash = {d5a2e0e8a77033834b1215019406a904},
issn = {0021-9258 (Print) 0021-9258 (Linking)},
journal = {J Biol Chem},
keywords = {Antibody Binding Calcium Cell Channels, Deletion Fluorescent Gene Humans Immunoblotting L-Type/*chemistry/metabolism/physiology Ligands Line Membrane/metabolism Mutagenesis, Patch-Clamp Precipitin Proline/chemistry Protein Site-Directed Structure, Technique Techniques Tertiary Tests Transfection},
month = {Aug 18},
note = {Gao, T Bunemann, M Gerhardstein, B L Ma, H Hosey, M M HL 23306/HL/NHLBI
NIH HHS/United States Research Support, Non-U.S. Gov't Research Support,
U.S. Gov't, P.H.S. United states The Journal of biological chemistry
J Biol Chem. 2000 Aug 18;275(33):25436-44.},
number = 33,
pages = {25436-44},
shorttitle = {Role of the C terminus of the alpha 1C (CaV1.2) subunit in membrane
targeting of cardiac L-type calcium channels},
timestamp = {2010-12-14T18:12:11.000+0100},
title = {Role of the C terminus of the alpha 1C (CaV1.2) subunit in membrane
targeting of cardiac L-type calcium channels},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10816591},
volume = 275,
year = 2000
}