Reactome | SLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular region

SLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular region

Stable Identifier

R-HSA-426155

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

K+/Cl- cotransport

ReviewStatus

5/5

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SLC12A4,5,6,7 cotransport K+, Cl- from cytosol to extracellular region

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K+/Cl- cotransport is implicated not only in regulatory volume decrease, but also in transepithelial salt absorption, renal K+ secretion, myocardial K+ loss during ischemia and regulation of neuronal Cl- concentration. Four genes (SLC12A4-7) encode the K+/Cl- cotransporters KCC1-4 respectively. Cotransport of K+ and Cl- is electroneutral with a 1:1 stoichiometry. These cotransporters function as homomultimers or heteromultimers with other K+/Cl- cotransporters.
SLC12A4 encodes KCC1 (Gillen CM et al, 1996). KCC1 is ubiquitously expressed, suggesting a housekeeping role in the regulation of cell volume. SLC12A5 encodes KCC2 (Song L et al, 2002). KCC2's expression is restricted to neurons in the CNS and retina. It is thought KCC2 is important for Cl- homeostasis in neurons. SLC12A6 encodes KCC3 (Race JE et al, 1999; Mount DB et al, 1999). KCC3 is highly expressed in heart, brain, spinal cord, kidney, muscle, pancreas and placenta. Defects in SLC12A6 are a cause of agenesis of the corpus callosum with peripheral neuropathy (ACCPN) (Howard HC et al, 2002). SLC12A7 encodes KCC4 (Mount DB et al, 1999) which is widely expressed, especially in the kidney. It is thought to play a role in transepithelial transport of Cl- by the proximal tubule.

Literature References

PubMed ID	Title	Journal	Year
8663127	Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family Gillen, CM, Brill, S, Forbush B, 3rd, Payne, JA	J Biol Chem	1996
10347194	Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family Delpire, E, Mount, DB, George AL, Jr, Xu, J, Song, L, Mercado, A, Gamba, G	J Biol Chem	1999
12106695	Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter Xie, Q, Mount, DB, George AL, Jr, Vázquez, N, Desai, R, Mercado, A, Song, L, Gamba, G	Brain Res Mol Brain Res	2002
10600773	Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter Holtzman, EJ, Dunham, PB, Wilson, FH, Makhlouf, FN, Race, JE, Logue, PJ	Am J Physiol	1999
12368912	The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum Simonati, A, Prévost, C, Siesser, WB, Zhan, FQ, Lemcke, B, Lu, J, Byun, N, Rochefort, D, Mercado, A, Song, L, Dupré, N, Rouleau, GA, Delpire, E, Welch, R, Horst, J, Fan, X, Mount, DB, Howard, HC, Rivière, JB, George AL, Jr, McDonald, MP, Bouchard, JP, England, R, Mathieu, J	Nat Genet	2002