Tmem16F forms a Ca2+-Activated Cation Channel Required for Lipid Scrambling in Platelets during Blood Coagulation

Yang, Huanghe; Kim, Andrew; David, Tovo; Palmer, Daniel; Jin, Taihao; Tien, Jason; Huang, Fen; Cheng, Tong; Coughlin, Shaun R.; Jan, Yuh Nung

doi:10.1016/j.bpj.2012.11.2033

Cited by 104 publications

(250 citation statements)

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“…In addition, TMEM16A and its close homolog TMEM16B contribute to nervous system functions ranging from the modulation of signal transduction in sensory neurons to the control of action potential duration in hippocampal neurons (4,5). Another member of this family, TMEM16F, is a small-conductance calcium-activated nonselective cation channel that is important for a calcium-activated scramblase activity associated with Scott syndrome's defects in blood coagulation (6,7).…”

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confidence: 99%

Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC)

Tien

Lee

Minor

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Transmembrane proteins with unknown function 16 (TMEM16A) is a calcium-activated chloride channel (CaCC) important for neuronal, exocrine, and smooth muscle functions. TMEM16A belongs to a family of integral membrane proteins that includes another CaCC, TMEM16B, responsible for controlling action potential waveform and synaptic efficacy, and a small-conductance calcium-activated nonselective cation channel, TMEM16F, linked to Scott syndrome. We find that these channels in the TMEM16 family share a homodimeric architecture facilitated by their cytoplasmic N termini. This dimerization domain is important for channel assembly in eukaryotic cells, and the in vitro association of peptides containing the dimerization domain is consistent with a homotypic protein–protein interaction. Amino acid substitutions in the dimerization domain affect functional TMEM16A-CaCC channel expression, as expected from its critical role in channel subunit assembly.

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confidence: 99%

Identification of a dimerization domain in the TMEM16A calcium-activated chloride channel (CaCC)

Tien

Lee

Minor

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…A splice form of Ano6 was identified that was associated with metastatic capability of mammary cancers in mouse and was related to poor prognosis of patients with breast cancer [54]. Notably, Ano6 has recently been associated with membrane phospholipid scrambling and cell shrinkage and therefore seems to be correlated to apoptosis rather than proliferation and cancer [55][56][57][58][59]. The distribution of lipids in the outer and inner leaflets of plasma membranes is asymmetrical: while phosphatidylcholine is mainly found in the outer leaflet, phosphatidylserine is present in the inner surface.…”

Section: Other Anoctamins Correlated To Cancermentioning

confidence: 99%

Role of anoctamins in cancer and apoptosis

Wanitchakool

Wolf

Koehl

et al. 2014

Phil. Trans. R. Soc. B

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Anoctamin 1 (TMEM16A, Ano1) is a recently identified Ca 2+ -activated chloride channel and a member of a large protein family comprising 10 paralogues. Before Ano1 was identified as a chloride channel protein, it was known as the cancer marker DOG1. DOG1/Ano1 is expressed in gastrointestinal stromal tumours (GIST) and particularly in head and neck squamous cell carcinoma, at very high levels never detected in other tissues. It is now emerging that Ano1 is part of the 11q13 locus, amplified in several types of tumour, where it is thought to augment cell proliferation, cell migration and metastasis. Notably, Ano1 is upregulated through histone deacetylase (HDAC), corresponding to the known role of HDAC in HNSCC. As Ano1 does not enhance proliferation in every cell type, its function is perhaps modulated by cell-specific factors, or by the abundance of other anoctamins. Thus Ano6, by regulating Ca 2+ -induced membrane phospholipid scrambling and annexin V binding, supports cellular apoptosis rather than proliferation. Current findings implicate other cellular functions of anoctamins, apart from their role as Ca 2+ -activated Cl − channels.

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“…In particular, we and others showed that TMEM16F is ubiquitously expressed in various cells, including hematopoietic cells, and is involved in the phosphatidylserine (PS) exposure on activated platelets required for blood clotting (9,11,12). TMEM16F is expressed in osteoblasts and was recently shown to be involved in mineralized bone matrix production during skeletal development (13).…”

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