anti-Solute Carrier Family 12 (Potassium-Chloride Transporter) Member 6 (SLC12A6) Antikörper

Human Solute Carrier Family 12 (Potassium-Chloride Transporter) Member 6 (SLC12A6) Interaktionspartner

1. we present the first Mexican patients with hereditary motor and sensory neuropathy with agenesis of the corpus callosum and a novel heterozygous frameshift variant, c.2097du p or p.(Trp700Leufs*19) of the SLC12A6 gene

2. Neurodegenerative deficits in hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.

3. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration.

4. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC.

5. SPAK may promote KCC3-mediated cervix tumor aggressiveness via the NF-kappaB/p38 MAPK/MMP2 axis.

6. SLC12A6 has been shown to be causative in Andermann Syndrome.

7. serine residue 96 of human KCC3 is a third site that has to be dephosphorylated for full activation of the cotransporter during hypotonicity.

8. mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations.

9. Neuropathic features of hereditary motor and sensory neuropathy/agenesis of corpus callosum in transgenic mouse lines are predominantly due to a neuronal KCC3 deficit, while the auditory impairment is due to loss of non-neuronal KCC3 expression.

10. The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions.

11. KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 that could result in modulation of KCC activity

12. mutations of the KCC3 gene may result in non-syndromic childhood onset of demyelinating hereditary motor and sensory neuropathy

13. human osteoblasts express functional K-Cl cotransporters in their cell membrane that seem to be able to induce the indirect activation of volume-sensitive Cl- channels by KCl through an increase in the intracellular ions, water influx and cell swelling.

14. all of the CCCs examined (NKCC1, NKCC2, KCC1, KCC3, and KCC4) can promote NH4(+) translocation, presumably through binding of the ion at the K(+) site

15. KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers.

16. Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome.

17. Among patients with early-stage node-negative breast cancer, disease-free survival (DFS) and overall survival (OS) curves were significantly different based on IGF-1 and KCC expression.

18. KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin.

19. KCC3 down-regulates E-cadherin/beta-catenin complex formation by inhibiting transcription of E-cadherin gene and accelerating proteosome-dependent degradation of beta-catenin protein

20. study provides evidence that the upstream SLC12A6 G/A promoter SNP is functional not only by changing the DNA primary structure but also by influencing the allelic epigenotype and consequently by influencing the chromatin organization

Mouse (Murine) Solute Carrier Family 12 (Potassium-Chloride Transporter) Member 6 (SLC12A6) Interaktionspartner

1. Results reveal the role of electrical activity in the process of neuromuscular junction (NMJ) denervation and subsequent neurodegeneration in Andermann syndrome. Study found that loss of KCC3 function is associated with an abnormal intrinsic neuronal electrical activity. Notably, we show that pharmacologically decreasing the firing frequency of Slc12a6-/- motoneurons partially rescues innervation at the NMJ.

2. electrophysiological studies using the threshold tracking technique indicated a reduced stimulus-response curve slope with an elevated rheobase, a decreased strength-duration time constant, diminished persistent Na(+) currents, and an outward deviation of threshold electrotonus in KCC3(-/-) nerves compared to wild-type nerves

3. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration.

4. Kcc3 inactivation caused systemic vascular resistance and ventricular mass to increase while preventing extracellular fluid volume to accumulate.

5. The results establish that the parvalbumin-positive neuronal population is an important player in the pathogenic development of peripheral neuropathy associated with agenesis of the corpus callosum.

6. Data are consistent with a role for KCC3 in the proximal tubule glucose reabsorption mechanism.

7. KCC3 regulates NADPH oxidase activity and neutrophils activation

8. KCC3 contributes to Cl(-) extrusion in adult sensory neurons

9. K+-Cl-cotransporter KCC3 is expressed in neurons, interneurons and radial glial-like cells in the spinal cord.

10. KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 that could result in modulation of KCC activity

11. This study demonstrated that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves.

12. Expression of Slc12a6 in the mouse nucleus accumbens is modulated by a sequence variant (B2 SINE indel) in the 3' UTR of Comt (catechol-O-methyltransferase).

13. SLC12A6 has a role in the development and maintenance of the nervous system

14. Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1) with the cotransporters KCC3, NKCC1, and NKCC2 but not KCC1 and KCC4

15. Deletion of this gene in mice causes deafness, neurodegeneration and reduced seizure threshold.

16. Based on microarray data and the known function of genes identified, Slc12a6 was selected as the primary candidate gene in Giant axonopathy mice; a 17-base deletion was detected from within exon 4 of Slc12a6.

17. Disruption of the KCC3 gene in mice produces an animal model of hypertension and polydipsia.