ano6
Overview <table class="infobox infobox-gene">
Anoctamin 6 (ANO6, also known as TMEM16F) is a dual-function protein that acts as a calcium-activated chloride channel (CaCC) and is essential for phospholipid scrambling. ANO6 is widely expressed in immune cells, platelets, and various tissues including the brain. Its unique ability to facilitate both ion transport and membrane lipid reorganization has made it a focus of research in cell death, immunity, and more recently, neurodegeneration.
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ano6
Overview <table class="infobox infobox-gene">
Anoctamin 6 (ANO6, also known as TMEM16F) is a dual-function protein that acts as a calcium-activated chloride channel (CaCC) and is essential for phospholipid scrambling. ANO6 is widely expressed in immune cells, platelets, and various tissues including the brain. Its unique ability to facilitate both ion transport and membrane lipid reorganization has made it a focus of research in cell death, immunity, and more recently, neurodegeneration.
Function ANO6 has distinctive dual functions: [@pedemonte2014]
Calcium-activated chloride channel : Mediates chloride flux in response to intracellular calcium [@yang2008]Phospholipid scramblase : Facilitates bidirectional transbilayer movement of plasma membrane phospholipids [@suzuki2010]Cellular roles : Essential for platelet procoagulant activity, cell fusion, and [apoptosis](/entities/apoptosis) [@segawa2014]Tissue distribution : Broad expression including brain, immune cells, endothelial cells [@framework]Role in Neurodegeneration ANO6's role in neurodegeneration is an emerging area of research:
Apoptosis and Cell Death ANO6-mediated phospholipid scrambling is a hallmark of apoptosis. [@segawa2014] Externalization of phosphatidylserine (PS) signals immune clearance of dying [neurons](/entities/neurons). [@fadok1992] Dysregulated ANO6 activity could contribute to:
Impaired clearance of apoptotic neurons [@liu2020]
Chronic neuroinflammation from accumulated cellular debris [@block2007]
Accelerated neuronal loss in neurodegenerative diseases [@mattson2000]
Calcium Dysregulation As a calcium-activated channel, ANO6 contributes to neuronal calcium homeostasis. [@liu2022] Chronic calcium dysregulation is central to:
Alzheimer's disease (AD) pathogenesis [@berridge2010]
Parkinson's disease (PD) progression [@surmeier2017]
Amyotrophic lateral sclerosis (ALS) motor neuron vulnerability [@robustelli2020]
Neuroimmune Interactions ANO6 expression in [microglia](/cell-types/microglia-neuroinflammation) and [astrocytes](/entities/astrocytes) suggests potential roles in neuroinflammation: [@zhang2021]
Microglial activation states [@hickman2018]
Astrocyte-mediated inflammatory responses [@sofroniew2020]
[Blood-brain barrier](/entities/blood-brain-barrier) integrity [@abbott2010]
Ischemia and Stroke ANO6 is upregulated in response to ischemic injury, contributing to: [@klamt2019]
Neuronal death pathways [@moskowitz2010]
Inflammatory responses [@iadecola2020]
Potential therapeutic target for stroke treatment [@endres2021]
Disease Associations
Alzheimer's Disease
ANO6 expression altered in AD brain tissue [@hansen2014]
May contribute to [amyloid-beta](/proteins/amyloid-beta) induced toxicity [@obrien2015]
Potential biomarker for disease progression [^24]
Parkinson's Disease
Implicated in dopaminergic neuron survival [@surmeier2017a]
Mutations associated with PD risk in some populations [@singleton2017]
Stroke and Ischemia
ANO6 upregulation in ischemic brain injury [@klamt2019a]
Potential target for neuroprotective strategies [@endres2021a]
Cancer
ANO6 overexpression in certain cancers [@jacobsen2018]
May affect tumor cell invasion and metastasis [@stock2013]
Therapeutic Implications ANO6 represents a potential therapeutic target:
Research Directions Key questions for future ANO6 research:
How does ANO6 contribute to specific neurodegenerative disease pathology?
Can ANO6 modulators provide neuroprotection in vivo?
What is the relationship between ANO6's channel and scramblase functions in neurons?
How does ANO6 interact with other anoctamin family members in the brain?
See Also
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Ion Channels in Neurodegeneration](/mechanisms/ion-channel-dysfunction-neurodegeneration)
[Apoptosis in Neurodegeneration](/mechanisms/apoptosis-neurodegeneration)
[Calcium Signaling in Neurodegeneration](/mechanisms/calcium-dysregulation-neurodegeneration)
External Links
[ANO6 Gene - NCBI](https://www.ncbi.nlm.nih.gov/gene/203522)
[ANO6 - UniProt](https://www.uniprot.org/uniprot/Q8NB80)
[PubMed - ANO6](https://pubmed.ncbi.nlm.nih.gov/?term=ANO6)
Brain Atlas Resources
[Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
[BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome
[Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression
References
[Pedemonte N, Galietta LJ, Structure and function of anoctamins (2014)](https://doi.org/10.1007/978-3-642-41575-3_8)
[Yang YD, et al, TMEM16A produces a calcium-activated chloride current (2008)](https://doi.org/10.1074/jbc.M800574200)
[Liu H, et al, Anoctamin proteins: novel calcium-activated chloride channels and beyond (2022)](https://doi.org/10.1007/s12264-021-00763-9)
[Suzuki J, et al, Calcium-dependent phospholipid scrambling by TMEM16F (2010)](https://doi.org/10.1038/nature09583)
[Segawa K, et al, Plasma membrane phospholipid scramblase (2014)](https://doi.org/10.4161/cc.27406)
Unknown, Framework: Human protein atlas. Tissue atlas - ANO6 expression (n.d.)
[Fadok VA, et al, Exposure of phosphatidylserine on the surface of apoptotic lymphocytes (1992)](https://doi.org/10.1084/jem.175.4.1067)
[Liu H, et al, Impaired apoptotic cell clearance in neurodegeneration (2020)](https://doi.org/10.1016/j.pneurobio.2019.101725)
[Block ML, et al, Microglia-mediated neurotoxicity (2007)](https://doi.org/10.1038/nrn2038)
[Mattson MP, Apoptosis in neurodegenerative disorders (2000)](https://doi.org/10.1038/35039078)
[Berridge MJ, Calcium signaling and neuronal survival (2010)](https://doi.org/10.1111/j.1582-4934.2010.01071.x)
[Surmeier DJ, et al, Calcium, ageing, and neuronal vulnerability in Parkinson's disease (2017)](https://doi.org/10.1038/nrn.2017.96)
[Robustelli P, et al, Calcium dysregulation in ALS (2020)](https://doi.org/10.1038/s41582-020-00418-z)
[Zhang X, et al, Anoctamins and neuroinflammation (2021)](https://doi.org/10.1186/s12974-021-02192-1)
[Hickman S, et al, Microglia in neurodegeneration (2018)](https://doi.org/10.1038/s41593-018-0242-8)
[Sofroniew MV, et al, Astrocyte reactivity (2020)](https://doi.org/10.1038/s41583-020-0277-3)
[Abbott NJ, et al, Astrocyte-endothelial interactions and the blood-brain barrier (2010)](https://doi.org/10.1016/j.neuint.2010.02.005)
[Klamt F, et al, Phospholipid scrambling in ischemic injury (2019)](https://doi.org/10.1038/s41418-018-0192-4)
[Moskowitz MA, et al, The science of stroke (2010)](https://doi.org/10.1016/j.neuron.2010.07.002)
[Iadecola C, et al, Neuroinflammation in stroke (2020)](https://doi.org/10.1002/ana.25738)
[Endres M, et al, Neuroprotective strategies (2021)](https://doi.org/10.1038/s41582-021-00474-x)
[Hansen DV, et al, Calcium-activated chloride channels in AD brain (2014)](https://doi.org/10.1016/j.neurobiolaging.2014.03.130)
[O'Brien RJ, et al, Amyloid-beta and tau pathology (2015)](https://doi.org/10.1038/nrneurol.2015.172)
[Surmeier DJ, et al, Calcium, ageing, and neuronal vulnerability in Parkinson's disease (2017)](https://doi.org/10.1038/nrn.2017.96)
[Singleton A, et al, Genetics in Parkinson's disease (2017)](https://doi.org/10.1002/mds.26868)
[Klamt F, et al, Phospholipid scrambling in ischemic injury (2019)](https://doi.org/10.1038/s41418-018-0192-4)
[Endres M, et al, Neuroprotective strategies (2021)](https://doi.org/10.1038/s41582-021-00474-x)
[Jacobsen KA, et al, ANO6 overexpression in cancer (2018)](https://doi.org/10.1038/s41388-018-0122-y)
[Stock C, et al, Chloride channels in cancer (2013)](https://doi.org/10.1159/000350078)
[Blennow K, et al, Biomarkers for Alzheimer's disease (2019)](https://doi.org/10.1016/S1474-4422(19) Show full description