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Review
. 2024 Jun:120:102888.
doi: 10.1016/j.ceca.2024.102888. Epub 2024 Apr 17.

VSI: The anoctamins: Structure and function: "Intracellular" anoctamins

Karl Kunzelmann  1 , Jiraporn Ousingsawat  2 , Rainer Schreiber  2
Affiliations
Free article
Review

VSI: The anoctamins: Structure and function: "Intracellular" anoctamins

Karl Kunzelmann et al. Cell Calcium. 2024 Jun.
Free article

Abstract

Plasma membrane localized anoctamin 1, 2 and 6 (TMEM16A, B, F) have been examined in great detail with respect to structure and function, but much less is known about the other seven intracellular members of this exciting family of proteins. This is probably due to their limited accessibility in intracellular membranous compartments, such as the endoplasmic reticulum (ER) or endosomes. However, these so-called intracellular anoctamins are also found in the plasma membrane (PM) which adds to the confusion regarding their cellular role. Probably all intracellular anoctamins except of ANO8 operate as intracellular phospholipid (PL) scramblases, allowing for Ca2+-activated, passive transport of phospholipids like phosphatidylserine between both membrane leaflets. Probably all of them also conduct ions, which is probably part of their physiological function. In this brief overview, we summarize key findings on the biological functions of ANO3, 4, 5, 7, 8, 9 and 10 (TMEM16C, D, E, G, H, J, K) that are gradually coming to light. Compartmentalized regulation of intracellular Ca2+ signals, tethering of the ER to specific PM contact sites, and control of intracellular vesicular trafficking appear to be some of the functions of intracellular anoctamins, while loss of function and abnormal expression are the cause for various diseases.

Keywords: ANO10; ANO3; ANO4; ANO5; ANO7; ANO8; ANO9; Calcium signaling; Chronic kidney disease; Dystonia; TMEM16C; TMEM16D; TMEM16E; TMEM16G; TMEM16H; TMEM16J; TMEM16K.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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