Sirianant, Lalida and Ousingsawat, Jiraporn and Tian, Yuemin and Schreiber, Rainer and Kunzelmann, Karl (2014) TMC8 (EVER2) attenuates intracellular signaling by Zn2+ and Ca2+ and suppresses activation of Cl- currents. CELLULAR SIGNALLING, 26 (12). pp. 2826-2833. ISSN 0898-6568, 1873-3913
Full text not available from this repository. (Request a copy)Abstract
Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1,TMEM16A). Ano1 is a Ca2+ activated Cl- channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and 8 (EVER1, EVER2) cause epidermodysplasia verruciformis. This rare skin disease is characterized by abnormal susceptibility to HPV infection and cancer. We found that in contrast to Ano1 the common paralogues TMC4-TMC8 did not produce Ca2+ activated Cl- currents when expressed in HEK293 cells. On the contrary, TMC8 was found to be localized in the endoplasmic reticulum (ER), where it inhibited receptor mediated Ca2+ release, activation of Ano1 and volume regulated LRRC8-related Cl- currents. Zn2+ is co-released from the ER together with Ca2+ and thereby further augments Ca2+ store release. Because TMC8 is required to lower cytosolic Zn2+ concentrations by the Zn2+ transporter ZnT-1, we hypothesize that HPV infections and cancer caused by mutations in TMC8 are related to upregulated Zn2+/Ca2+ signaling and activation of Ano1. (C) 2014 Elsevier Inc All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SQUAMOUS-CELL CARCINOMA; REGULATED ANION CHANNEL; ESSENTIAL COMPONENT; CANCER PROGRESSION; VOLUME REGULATION; MOUSE ASTROCYTES; MEMBRANE-PROTEIN; TMEM16A; EXPRESSION; FAMILY; Transmembrane channel-like protein; TMC8; EVER2; Zn2+ signaling; LRRC8A; Anoctamin 1 |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Aug 2019 09:50 |
| Last Modified: | 07 Aug 2019 09:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9158 |
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