dc.contributor.author | Adragna, Norma C. | en_US |
dc.contributor.author | Ravilla, Nagendra B. | en_US |
dc.contributor.author | Lauf, Peter K. | en_US |
dc.contributor.author | Begum, Gulnaz | en_US |
dc.contributor.author | Khanna, Arjun R. | en_US |
dc.contributor.author | Sun, Dandan | en_US |
dc.contributor.author | Kahle, Kristopher T. | en_US |
dc.date.accessioned | 2015-08-03T14:01:30Z | |
dc.date.issued | 2015 | en_US |
dc.identifier.citation | Adragna, Norma C., Nagendra B. Ravilla, Peter K. Lauf, Gulnaz Begum, Arjun R. Khanna, Dandan Sun, and Kristopher T. Kahle. 2015. “Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis.” Frontiers in Cellular Neuroscience 9 (1): 255. doi:10.3389/fncel.2015.00255. http://dx.doi.org/10.3389/fncel.2015.00255. | en |
dc.identifier.issn | 1662-5102 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820780 | |
dc.description.abstract | The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K+ and Cl− efflux via activation of K+ channels, volume-regulated anion channels (VRACs), and the K+-Cl− cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na+-K+-2Cl− cotransporter isoform 1 (NKCC1). This results in a rapid (<10 min) and significant (>90%) reduction in intracellular K+ content (Ki) via both Cl-dependent (KCC3a + NKCC1) and Cl-independent [DCPIB (VRAC inhibitor)-sensitive] pathways, which collectively renders cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD. | en |
dc.language.iso | en_US | en |
dc.publisher | Frontiers Media S.A. | en |
dc.relation.isversionof | doi:10.3389/fncel.2015.00255 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496573/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | K-Cl cotransporters | en |
dc.subject | KCC3 | en |
dc.subject | NKCC1 | en |
dc.subject | SPAK | en |
dc.subject | cell volume homeostasis | en |
dc.subject | regulatory volume decrease | en |
dc.subject | cerebral edema | en |
dc.subject | neurodegeneration | en |
dc.title | Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Frontiers in Cellular Neuroscience | en |
dash.depositing.author | Khanna, Arjun R. | en_US |
dc.date.available | 2015-08-03T14:01:30Z | |
dc.identifier.doi | 10.3389/fncel.2015.00255 | * |
dash.contributor.affiliated | Khanna, Arjun | |
dash.contributor.affiliated | Kahle, Kristopher T. | |