Mattheij, Nadine J. A. and Braun, Attila and van Kruchten, Roger and Castoldi, Elisabetta and Pircher, Joachim and Baaten, Constance C. F. M. J. and Wuelling, Manuela and Kuijpers, Marijke J. E. and Koehler, Ralf and Poole, Alastair W. and Schreiber, Rainer and Vortkamp, Andrea and Collins, Peter W. and Nieswandt, Bernhard and Kunzelmann, Karl and Cosemans, Judith M. E. M. and Heemskerk, Johan W. M. (2016) Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage. FASEB JOURNAL, 30 (2). pp. 727-737. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
Scott syndrome is a rare bleeding disorder, characterized by altered Ca2+-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano) 6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca2+-dependent K(Ca)3.1Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6min (control 6.4min, P< 0.05). Platelets from the surviving Ano6-deficient mice resembled platelets from patients with Scott syndrome in: 1) normal collagen-induced aggregate formation (P > 0.05) with reduced PS exposure (265 to 90%); 2) lowered Ca2+-dependent swelling (280%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THROMBUS FORMATION; SCOTT SYNDROME; PHOSPHATIDYLSERINE EXPOSURE; PROCOAGULANT RESPONSE; CHLORIDE CHANNEL; LIPID SCRAMBLASE; GLYCOPROTEIN-VI; BLOOD-CELLS; TMEM16F; COAGULATION; bleeding; embryonic lethality; phosphatidylserine; Scott syndrome; TMEM16F |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Mar 2019 07:12 |
| Last Modified: | 14 Mar 2019 07:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2462 |
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