Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel

Reichhart, Nadine; Schöberl, Simon; Keckeis, Susanne; Alfaar, Ahmad Samir; Cordes, Magdalena; Crespo-Garcia, Sergio; Haeckel, Akvile; Kociok, Norbert; Föckler, Renate; Fels, Gabriele; Mataruga, Anja; Rauh, R. D.; Milenkovic, Vladimir M.; Zühlke, Kerstin; Klussmann, Enno; Schellenberger, Eyk; Strauß, Olaf

doi:10.1038/s41598-018-37287-y

Cited by 29 publications

(23 citation statements)

References 30 publications

(39 reference statements)

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“…Capillary pericytes also express other anoctamins that have been implicated in lipid scrambling: Ano4 and Ano6, as well as the poorly understood Ano10 (He et al, 2018;Vanlandewijck et al, 2018). Reports indicate that Ano6 may act as a Ca 2+ -activated Cl − and non-selective cation channel with scramblase activity (Suzuki et al, 2010;Yang et al, 2012;Grubb et al, 2013) and Ano4 was recently shown to be a Ca 2+dependent non-specific cation channel with similar scrambling capabilities (Reichhart et al, 2019).…”

Section: Pericyte CL − Channelsmentioning

confidence: 99%

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

Hariharan

Weir

Robertson

et al. 2020

Front. Cell. Neurosci.

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Brain pericytes reside on the abluminal surface of capillaries, and their processes cover ~90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth, 1871; Rouget, 1873) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for Gs-coupled GPCRs and ATP-sensitive potassium (KATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and Gq, Gi/o, and G12/13 signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease.

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Section: Pericyte CL − Channelsmentioning

confidence: 99%

The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

Hariharan

Weir

Robertson

et al. 2020

Front. Cell. Neurosci.

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“…1 and 3 and Table 4) are consistent with the distinct pathogenic processes between these two diseases. ANO4 is a calcium-dependent non-selective cation channel involved in Ca ++ regulation within the endoplasmic reticulum (ER) and Ca ++ dependent plasma membrane lipid scramblase activity [43,44]. Expression of ANO4 attenuates Ca ++ leakage from the ER [44].…”

Section: Discussionmentioning

confidence: 99%

Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones

Jayachandran

Yuzhakov

Kumar

et al. 2020

Orphanet J Rare Dis

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Background Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process. Methods Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m2 were studied. Urinary EVs were quantified by digital flow cytometer and results expressed as EVs/ mg creatinine. Expressions of urinary proteins were measured by customized antibody array and results expressed as relative intensity. Data were analyzed by ANCOVA adjusting for sex, and biomarkers differences were considered statistically significant among groups at a false discovery rate threshold of Q < 0.20. Results Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q < 0.20) altered among PH1 patients without NC and KS, patients with NC or patients with KS alone. Three cellular adhesion/inflammatory (ICAM-1, MCP-1, and tissue factor) markers carrying EVs were statistically (Q < 0.20) different between PH1 patients groups. Three renal injury (β2-microglobulin, laminin α5, and NGAL) marker-positive urinary EVs out of 5 marker assayed were statistically (Q < 0.20) different among PH1 patients without and with NC or KS. The number of immune/inflammatory cell-derived (8 different cell markers positive) EVs were statistically (Q < 0.20) different between PH1 patients groups. EV generation markers (ANO4 and HIP1) and renal calcium/phosphate regulation or calcifying matrixvesicles markers (klotho, PiT1/2) were also statistically (Q < 0.20) different between PH1 patients groups. Only 13 (CD14, CD40, CFVII, CRP, E-cadherin, EGFR, endoglin, fetuin A, MCP-1, neprilysin, OPN, OPGN, and PDGFRβ) out of 40 proteins were significantly (Q < 0.20) different between PH1 patients without and with NC or KS. Conclusions These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.

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“…Four single membrane-pass auxiliary subunits of CaCCs have been identified (known as Ca 2+ -activated Cl − channel regulator or Cl − channel accessory [CLCA]1-4) [ 290 , 291 ]. Interestingly, the molecular identities of the conducting subunits were only discovered later and termed Best1-4 and TMEM16 [ [292] , [293] , [294] , [295] ]. CaCCs demonstrate voltage-dependence at steady-state, which is abolished following an increase in [Ca 2+ ] i [ 296 ].…”

Section: − Channelsmentioning

confidence: 99%