Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions.

The Journal of Biological Chemistry
Raul E GuzmanChristoph Fahlke

Abstract

ClC-3 is a member of the CLC family of anion channels and transporters, for which multiple functional properties and subcellular localizations have been reported. Since alternative splicing often results in proteins with diverse properties, we investigated to what extent alternative splicing might influence subcellular targeting and function of ClC-3. We identified three alternatively spliced ClC-3 isoforms, ClC-3a, ClC-3b, and ClC-3c, in mouse brain, with ClC-3c being the predominant splice variant. Whereas ClC-3a and ClC-3b are present in late endosomes/lysosomes, ClC-3c is targeted to recycling endosomes via a novel N-terminal isoleucine-proline (IP) motif. Surface membrane insertion of a fraction of ClC-3c transporters permitted electrophysiological characterization of this splice variant through whole-cell patch clamping on transfected mammalian cells. In contrast, neutralization of the N-terminal dileucine-like motifs was required for functional analysis of ClC-3a and ClC-3b. Heterologous expression of ClC-3a or ClC-3b carrying mutations in N-terminal dileucine motifs as well as WTClC-3c in HEK293T cells resulted in outwardly rectifying Cl(-) currents with significant capacitive current components. We conclude that altern...Continue Reading

References

Nov 1, 1977·The Journal of General Physiology·F Bezanilla, C M Armstrong
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M StockerO Pongs
Nov 1, 1996·The Journal of Cell Biology·O UllrichR G Parton
Oct 18, 2000·The Journal of Biological Chemistry·C FahlkeA L George
Dec 26, 2000·The Journal of Biological Chemistry·M SchwakeT J Jentsch
Mar 29, 2001·The Journal of Biological Chemistry·P HuangD J Nelson
Apr 23, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takehiko OguraNobuya Inagaki
May 9, 2002·American Journal of Physiology. Cell Physiology·Xinhua LiSteven A Weinman
Jun 13, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Momono YoshikawaSei Sasaki
Mar 26, 2003·Annual Review of Biochemistry·Juan S Bonifacino, Linton M Traub
Mar 26, 2004·Nature Reviews. Molecular Cell Biology·Frederick R Maxfield, Timothy E McGraw
Jul 22, 2005·Nature·Alessandra Picollo, Michael Pusch
Oct 14, 2005·Journal of Cellular Physiology·Tatsunori SuzukiShinichi Uchida
Sep 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mallorie PoëtThomas J Jentsch
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tanja MaritzenThomas J Jentsch
Apr 15, 2009·The Journal of General Physiology·Alexi K Alekov, Christoph Fahlke
Oct 13, 2009·The Journal of Biological Chemistry·Loretta FerreraLuis J V Galietta
May 15, 2010·The Journal of Biological Chemistry·Ioana NeagoeThomas J Jentsch
May 27, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrew J Smith, Jonathan D Lippiat
Sep 8, 2010·The Journal of Biological Chemistry·Tobias Stauber, Thomas J Jentsch
Oct 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nathan J PavlosReinhard Jahn
Mar 8, 2011·Nature Neuroscience·Vladimir RiazanskiDeborah J Nelson
Jan 24, 2012·The Journal of Biological Chemistry·Matthias Grieschat, Alexi K Alekov
Jul 25, 2012·Biophysical Journal·Giovanni ZifarelliMichael Pusch
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Nov 21, 2012·The Journal of Physiology·Laurel M FarmerDeborah J Nelson
Mar 21, 2013·ACS Chemical Neuroscience·Raul E GuzmanAlexi K Alekov
Nov 21, 2013·Communicative & Integrative Biology·Hotaka Kobayashi, Mitsunori Fukuda

❮ Previous
Next ❯

Citations

Oct 4, 2017·The Journal of Biological Chemistry·Raul E GuzmanChristoph Fahlke
May 31, 2018·Physiological Reviews·Thomas J Jentsch, Michael Pusch
Jul 6, 2018·The Journal of Physiology·Raul E Guzman, Christoph Fahlke
Sep 19, 2019·American Journal of Physiology. Cell Physiology·Paul H SchlesingerDeborah J Nelson
Mar 3, 2020·The EMBO Journal·Stefanie WeinertThomas J Jentsch
May 12, 2020·EMBO Reports·Matthias GrieschatAlexi K Alekov
Apr 24, 2020·Frontiers in Neuroscience·Bettina U WilkeMichaela Kress
Aug 28, 2020·Frontiers in Physiology·Christoph Fahlke
Jan 1, 2021·Biochemical and Biophysical Research Communications·Satoshi YamadaHisao Yamamura
Mar 13, 2021·Frontiers in Cell and Developmental Biology·Shroddha BoseTobias Stauber
Aug 29, 2020·Bone·Paul H SchlesingerHarry C Blair
May 6, 2021·Epilepsia·Hailan HeTobias Stauber

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Toshiaki OkadaYasunobu Okada
FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Takehiko OguraNobuya Inagaki
Annals of the New York Academy of Sciences
J W Hanrahan, J A Tabcharani
© 2021 Meta ULC. All rights reserved