Regulation of the Ca2+-activated chloride channel Anoctamin-1 (TMEM16A) by Ca2+-induced interaction with FKBP12 and calcineurin

Sánchez-Solano, Alfredo; Corral, Nancy; Segura-Covarrubias, Guadalupe; Guzmán-Hernández, María Luisa; Aréchiga-Figueroa, Iván A.; Cruz-Rangel, Silvia; Pérez‐Cornejo, Patricia; Arreola, Jorge

doi:10.1016/j.ceca.2020.102211

Cited by 6 publications

(2 citation statements)

References 55 publications

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“…Currently, FKBP12 has been well studied in both S. cerevisiae [22,57,58] and human cell Fig. 5 Fold change of DEGs related to cellulose degradation that are categorized into four types: a cellulase; b nonenzymatic cellulose attacking enzymes; c hemicellulase, and d transcriptional factors [59][60][61]. It is supposed that T. reesei (filamentous fungus) should be more similar to S. cerevisiae (a model fungus) than human cells.…”

Section: Fkbp12 Is Required For the Temporary Inhibition Of Rapamycinmentioning

confidence: 99%

High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12

Pang

Wang

Zhang

et al. 2021

Biotechnol Biofuels

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Background Knowledge with respect to regulatory systems for cellulase production is prerequisite for exploitation of such regulatory networks to increase cellulase production, improve fermentation efficiency and reduce the relevant production cost. The target of rapamycin (TOR) signaling pathway is considered as a central signaling hub coordinating eukaryotic cell growth and metabolism with environmental inputs. However, how and to what extent the TOR signaling pathway and rapamycin are involved in cellulase production remain elusive. Result At the early fermentation stage, high-dose rapamycin (100 μM) caused a temporary inhibition effect on cellulase production, cell growth and sporulation of Trichoderma reesei RUT-C30 independently of the carbon sources, and specifically caused a tentative morphology defect in RUT-C30 grown on cellulose. On the contrary, the lipid content of T. reesei RUT-C30 was not affected by rapamycin. Accordingly, the transcriptional levels of genes involved in the cellulase production were downregulated notably with the addition of rapamycin. Although the mRNA levels of the putative rapamycin receptor trFKBP12 was upregulated significantly by rapamycin, gene trTOR (the downstream effector of the rapamycin–FKBP12 complex) and genes associated with the TOR signaling pathways were not changed markedly. With the deletion of gene trFKBP12, there is no impact of rapamycin on cellulase production, indicating that trFKBP12 mediates the observed temporary inhibition effect of rapamycin. Conclusion Our study shows for the first time that only high-concentration rapamycin induced a transient impact on T. reesei RUT-C30 at its early cultivation stage, demonstrating T. reesei RUT-C30 is highly resistant to rapamycin, probably due to that trTOR and its related signaling pathways were not that sensitive to rapamycin. This temporary influence of rapamycin was facilitated by gene trFKBP12. These findings add to our knowledge on the roles of rapamycin and the TOR signaling pathways play in T. reesei.

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Section: Fkbp12 Is Required For the Temporary Inhibition Of Rapamycinmentioning

confidence: 99%

High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12

Pang

Wang

Zhang

et al. 2021

Biotechnol Biofuels

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“…While direct a CAM-regulation of TMEM16A is discussed controversially, several studies demonstrate that CAM-dependent kinase II (CAMKII) regulates CaCC/TMEM16A. However, CAMKII was found to activate [ 8 , 9 , 10 , 11 , 12 ] and to inhibit [ 13 , 14 , 15 , 16 , 17 ] CaCC and TMEM16A, respectively. Greenwood and Leblanc found a cell-type-dependent activation/inhibition of CaCC by CAMKII [ 18 ], while Ko et al found differential regulation of TMEM16A by CAMKII, depending on the splice variant [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Calmodulin-Dependent Regulation of Overexpressed but Not Endogenous TMEM16A Expressed in Airway Epithelial Cells

et al. 2021

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Regulation of the Ca2+-activated Cl− channel TMEM16A by Ca2+/calmodulin (CAM) is discussed controversially. In the present study, we compared regulation of TMEM16A by Ca2+/calmodulin (holo-CAM), CAM-dependent kinase (CAMKII), and CAM-dependent phosphatase calcineurin in TMEM16A-overexpressing HEK293 cells and TMEM16A expressed endogenously in airway and colonic epithelial cells. The activator of the Ca2+/CAM-regulated K+ channel KCNN4, 1-EBIO, activated TMEM16A in overexpressing cells, but not in cells with endogenous expression of TMEM16A. Evidence is provided that CAM-interaction with TMEM16A modulates the Ca2+ sensitivity of the Cl− channel. Enhanced Ca2+ sensitivity of overexpressed TMEM16A explains its activity at basal (non-elevated) intracellular Ca2+ levels. The present results correspond well to a recent report that demonstrates a Ca2+-unbound form of CAM (apo-CAM) that is pre-associated with TMEM16A and mediates a Ca2+-dependent sensitization of activation (and inactivation). However, when using activators or inhibitors for holo-CAM, CAMKII, or calcineurin, we were unable to detect a significant impact of CAM, and limit evidence for regulation by CAM-dependent regulatory proteins on receptor-mediated activation of endogenous TMEM16A in airway or colonic epithelial cells. We propose that regulatory properties of TMEM16A and and other members of the TMEM16 family as detected in overexpression studies, should be validated for endogenous TMEM16A and physiological stimuli such as activation of phospholipase C (PLC)-coupled receptors.

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Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A)

Arreola

Pérez‐Cornejo

Segura-Covarrubias

et al. 2022

Anion Channels and Transporters

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Regulation of the Ca2+-activated chloride channel Anoctamin-1 (TMEM16A) by Ca2+-induced interaction with FKBP12 and calcineurin

Cited by 6 publications

References 55 publications

High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12

High-dose rapamycin exerts a temporary impact on T. reesei RUT-C30 through gene trFKBP12

Calmodulin-Dependent Regulation of Overexpressed but Not Endogenous TMEM16A Expressed in Airway Epithelial Cells

Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A)

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