Modulating Ca2+ signals: a common theme for TMEM16, Ist2, and TMC

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• 作者：Karl Kunzelmann ; Ines Cabrita…
• 关键词：TMEM16 proteins ; Anoctamin 1 ; Anoctamin 6 ; TMEM16A ; TMEM16F ; TMC ; nhTMEM16 ; Ca2+ signaling ; Ist2 ; Lipid rafts ; ER Ca2+ store ; SCP2 ; Secretion
• 刊名：Pfl¨¹gers Archiv - European Journal of Physiology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：468
• 期：3
• 页码：475-490
• 全文大小：1,830 KB
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• 作者单位：Karl Kunzelmann (1)
  Ines Cabrita (1)
  Podchanart Wanitchakool (1)
  Jiraporn Ousingsawat (1)
  Lalida Sirianant (1)
  Roberta Benedetto (1)
  Rainer Schreiber (1)
  
  1. Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

Since the discovery of TMEM16A (anoctamin 1, ANO1) as Ca2+-activated Cl− channel, the protein was found to serve different physiological functions, depending on the type of tissue. Subsequent reports on other members of the anoctamin family demonstrated a broad range of yet poorly understood properties. Compromised anoctamin function is causing a wide range of diseases, such as hearing loss (ANO2), bleeding disorder (ANO6), ataxia and dystonia (ANO3, 10), persistent borrelia and mycobacteria infection (ANO10), skeletal syndromes like gnathodiaphyseal dysplasia and limb girdle muscle dystrophy (ANO5), and cancer (ANO1, 6, 7). Animal models demonstrate CF-like airway disease, asthma, and intestinal hyposecretion (ANO1). Although present data indicate that ANO1 is a Ca2+-activated Cl− channel, it remains unclear whether all anoctamins form plasma membrane-localized or intracellular chloride channels. We find Ca2+-activated Cl− currents appearing by expression of most anoctamin paralogs, including the Nectria haematococca homologue nhTMEM16 and the yeast homologue Ist2. As recent studies show a role of anoctamins, Ist2, and the related transmembrane channel-like (TMC) proteins for intracellular Ca2+ signaling, we will discuss the role of these proteins in generating compartmentalized Ca2+ signals, which may give a hint as to the broad range of cellular functions of anoctamins. Keywords TMEM16 proteins Anoctamin 1 Anoctamin 6 TMEM16A TMEM16F TMC nhTMEM16 Ca2+ signaling Ist2 Lipid rafts ER Ca2+ store SCP2 Secretion