Membrane Proteins; Physiology; Sodium-Potassium-Chloride Symporters; Muscle Cells
Regulation of intracellular ion concentrations is essential to all living cells. The transport of ions mediated by specific membrane proteins underlies control of cell volume, epithelial transport, and the maintenance of transmembrane ion gradients which underlie electrical activity in nerve and muscle cells. Our work is directed towards understanding the mechanisms by which ion transport take place, and our attention is focused on a particular family of transport proteins, the cation-chloride cotransporters. Among these, the Na-K-Cl cotransporter uses the Na gradient to drive accumulation of cellular K and Cl and is a central element in the process of net salt transport in both secretory and absorptive epithelia. We are addressing questions of protein structure, of structure-function relationships, and of protein kinase-mediated regulation, in animal models and by expression of transport proteins in cell culture.
Speciailized Terms: Membrane Proteins; Epithelial Transport; Ion Transport; Na-K-Cl Cotransporter; Nerve Cells; Muscle Cells
Extensive Research Description
The residues determining differences in ion affinities among the alternative splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2).
Giménez I, Forbush B. The residues determining differences in ion affinities among the alternative splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2). The Journal Of Biological Chemistry 2007, 282:6540-7.
PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1).
Dowd BF, Forbush B. PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1). The Journal Of Biological Chemistry 2003, 278:27347-53.
Full List of PubMed Publications
- Corrie JE, Kaplan JH, Forbush B, Ogden DC, Trentham DR: Commentary on "Caged Phosphate and the Slips and Misses in Determination of Quantum Yields for Ultraviolet-A-Induced Photouncaging" by G. Gasser and Co-Workers. Chemphyschem. 2015 Jun 22; 2015 Feb 20. PMID: 25704071
- Monette MY, Somasekharan S, Forbush B: Molecular motions involved in Na-K-Cl cotransporter-mediated ion transport and transporter activation revealed by internal cross-linking between transmembrane domains 10 and 11/12. J Biol Chem. 2014 Mar 14; 2014 Jan 22. PMID: 24451383
- Somasekharan S, Monette MY, Forbush B: Functional expression of human NKCC1 from a synthetic cassette-based cDNA: introduction of extracellular epitope tags and removal of cysteines. PLoS One. 2013; 2013 Dec 5. PMID: 24339991
- Somasekharan S, Tanis J, Forbush B: Loop diuretic and ion-binding residues revealed by scanning mutagenesis of transmembrane helix 3 (TM3) of Na-K-Cl cotransporter (NKCC1). J Biol Chem. 2012 May 18; 2012 Mar 21. PMID: 22437837
- Monette MY, Forbush B: Regulatory activation is accompanied by movement in the C terminus of the Na-K-Cl cotransporter (NKCC1). J Biol Chem. 2012 Jan 13; 2011 Nov 25. PMID: 22121194
- Monette MY, Rinehart J, Lifton RP, Forbush B: Rare mutations in the human Na-K-Cl cotransporter (NKCC2) associated with lower blood pressure exhibit impaired processing and transport function. Am J Physiol Renal Physiol. 2011 Apr; 2011 Jan 5. PMID: 21209010
- Leiserson WM, Forbush B, Keshishian H: Drosophila glia use a conserved cotransporter mechanism to regulate extracellular volume. Glia. 2011 Feb. PMID: 21125654
- Carmosino M, Rizzo F, Procino G, Basco D, Valenti G, Forbush B, Schaeren-Wiemers N, Caplan MJ, Svelto M: MAL/VIP17, a new player in the regulation of NKCC2 in the kidney. Mol Biol Cell. 2010 Nov 15; 2010 Sep 22. PMID: 20861303
- Flemmer AW, Monette MY, Djurisic M, Dowd B, Darman R, Gimenez I, Forbush B: Phosphorylation state of the Na+-K+-Cl- cotransporter (NKCC1) in the gills of Atlantic killifish (Fundulus heteroclitus) during acclimation to water of varying salinity. J Exp Biol. 2010 May. PMID: 20400641
- Tanis JE, Bellemer A, Moresco JJ, Forbush B, Koelle MR: The potassium chloride cotransporter KCC-2 coordinates development of inhibitory neurotransmission and synapse structure in Caenorhabditis elegans. J Neurosci. 2009 Aug 12. PMID: 19675228
- Rinehart J, Maksimova YD, Tanis JE, Stone KL, Hodson CA, Zhang J, Risinger M, Pan W, Wu D, Colangelo CM, Forbush B, Joiner CH, Gulcicek EE, Gallagher PG, Lifton RP: Sites of regulated phosphorylation that control K-Cl cotransporter activity. Cell. 2009 Aug 7. PMID: 19665974
- Carmosino M, Giménez I, Caplan M, Forbush B: Exon loss accounts for differential sorting of Na-K-Cl cotransporters in polarized epithelial cells. Mol Biol Cell. 2008 Oct; 2008 Jul 30. PMID: 18667527
- Pedersen M, Carmosino M, Forbush B: Intramolecular and intermolecular fluorescence resonance energy transfer in fluorescent protein-tagged Na-K-Cl cotransporter (NKCC1): sensitivity to regulatory conformational change and cell volume. J Biol Chem. 2008 Feb 1; 2007 Nov 28. PMID: 18045874
- Giménez I, Forbush B: The residues determining differences in ion affinities among the alternative splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2). J Biol Chem. 2007 Mar 2; 2006 Dec 23. PMID: 17186942
- Kahle KT, Gimenez I, Hassan H, Wilson FH, Wong RD, Forbush B, Aronson PS, Lifton RP: WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia. Proc Natl Acad Sci U S A. 2004 Feb 17; 2004 Feb 9. PMID: 14769928
- Dowd BF, Forbush B: PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1). J Biol Chem. 2003 Jul 25; 2003 May 9. PMID: 12740379
- Giménez I, Forbush B: Short-term stimulation of the renal Na-K-Cl cotransporter (NKCC2) by vasopressin involves phosphorylation and membrane translocation of the protein. J Biol Chem. 2003 Jul 18; 2003 May 5. PMID: 12732642
- Flemmer AW, Gimenez I, Dowd BF, Darman RB, Forbush B: Activation of the Na-K-Cl cotransporter NKCC1 detected with a phospho-specific antibody. J Biol Chem. 2002 Oct 4; 2002 Jul 26. PMID: 12145305
- Darman RB, Forbush B: A regulatory locus of phosphorylation in the N terminus of the Na-K-Cl cotransporter, NKCC1. J Biol Chem. 2002 Oct 4; 2002 Jul 26. PMID: 12145304
- Giménez I, Isenring P, Forbush B: Spatially distributed alternative splice variants of the renal Na-K-Cl cotransporter exhibit dramatically different affinities for the transported ions. J Biol Chem. 2002 Mar 15; 2002 Jan 28. PMID: 11815599