Hammer, Christian and Wanitchakool, Podchanart and Sirianant, Lalida and Papiol, Sergi and Monnheimer, Mathieu and Faria, Diana and Ousingsawat, Jiraporn and Schramek, Natalie and Schmitt, Corinna and Margos, Gabriele and Michel, Angelika and Kraiczy, Peter and Pawlita, Michael and Schreiber, Rainer and Schulz, Thomas F. and Fingerle, Volker and Tumani, Hayrettin and Ehrenreich, Hannelore and Kunzelmann, Karl (2015) A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity. MOLECULAR MEDICINE, 21. ISSN 1076-1551, 1528-3658
Full text not available from this repository. (Request a copy)Abstract
In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding Cl- channels and phospholipid scramblases. ANO10 augments volume-regulated Cl- currents (I-Hypo) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on I-Hypo, RVD and intracellular Ca2+ signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECESSIVE CEREBELLAR-ATAXIA; LYME-DISEASE; ESSENTIAL COMPONENT; CHLORIDE CHANNEL; MEMBRANE-PROTEIN; ANION CHANNELS; ANOCTAMIN 6; CELLS; SUSCEPTIBILITY; IDENTIFICATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Jul 2019 08:25 |
| Last Modified: | 31 Jul 2019 08:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6240 |
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