Tubulin Regulates Plasma Membrane Ca-ATPase Activity in a Lipid Environment-dependent Manner

Overview

Journal Cell Biochem Biophys

Specialties Biochemistry
Biophysics
Cell Biology

Date 2023 Dec 22

PMID 38133791

Authors

Noelia E Monesterolo

Veronica S Santander

Alexis N Campetelli

Juan F Rivelli Antonelli

Ayelen D Nigra

Melisa M Balach

Tamara Muhlberger

Gabriela Previtali

Cesar H Casale

Affiliations

Soon will be listed here.

Abstract

Ca plays a crucial role in cell signaling, cytosolic Ca can change up to 10,000-fold in concentration due to the action of Ca-ATPases, including PMCA, SERCA and SCR. The regulation and balance of these enzymes are essential to maintain cytosolic Ca homeostasis. Our laboratory has discovered a novel PMCA regulatory system, involving acetylated tubulin alone or in combination with membrane lipids. This regulation controls cytosolic Ca levels and influences cellular properties such as erythrocyte rheology. This review summarizes the findings on the regulatory mechanism of PMCA activity by acetylated tubulin in combination with lipids. The combination of tubulin cytoskeleton and membrane lipids suggests a novel regulatory system for PMCA, which consequently affects cytosolic Ca content, depending on cytoskeletal and plasma membrane dynamics. Understanding the interaction between acetylated tubulin, lipids and PMCA activity provides new insights into Ca signaling and cell function. Further research may shed light on potential therapeutic targets for diseases related to Ca dysregulation. This discovery contributes to a broader understanding of cellular processes and offers opportunities to develop innovative approaches to treat Ca-related disorders. By elucidating the complex regulatory mechanisms of Ca homeostasis, we advance our understanding of cell biology and its implications for human health.

References

Saffioti N, de Sautu M, Riesco A, Ferreira-Gomes M, Rossi J, Mangialavori I . Conformational changes during the reaction cycle of plasma membrane Ca2+-ATPase in the autoinhibited and activated states. Biochem J. 2021; 478(10):2019-2034. DOI: 10.1042/BCJ20210036. View

Brini M, Carafoli E, Cali T . The plasma membrane calcium pumps: focus on the role in (neuro)pathology. Biochem Biophys Res Commun. 2016; 483(4):1116-1124. DOI: 10.1016/j.bbrc.2016.07.117. View

Bruce J . Metabolic regulation of the PMCA: Role in cell death and survival. Cell Calcium. 2017; 69:28-36. PMC: 5761718. DOI: 10.1016/j.ceca.2017.06.001. View

Lisek M, Boczek T, Zylinska L . Calcium as a Trojan horse in mental diseases-The role of PMCA and PMCA-interacting proteins in bipolar disorder and schizophrenia. Neurosci Lett. 2017; 663:48-54. DOI: 10.1016/j.neulet.2017.08.005. View

Di Leva F, Domi T, Fedrizzi L, Lim D, Carafoli E . The plasma membrane Ca2+ ATPase of animal cells: structure, function and regulation. Arch Biochem Biophys. 2008; 476(1):65-74. DOI: 10.1016/j.abb.2008.02.026. View

Monesterolo N, Santander V, Campetelli A, Arce C, Barra H, Casale C . Activation of PMCA by calmodulin or ethanol in plasma membrane vesicles from rat brain involves dissociation of the acetylated tubulin/PMCA complex. FEBS J. 2008; 275(14):3567-79. DOI: 10.1111/j.1742-4658.2008.06502.x. View

Campetelli A, Previtali G, Arce C, Barra H, Casale C . Activation of the plasma membrane H-ATPase of Saccharomyces cerevisiae by glucose is mediated by dissociation of the H(+)-ATPase-acetylated tubulin complex. FEBS J. 2005; 272(22):5742-52. DOI: 10.1111/j.1742-4658.2005.04959.x. View

Muhlberger T, Balach M, Bisig C, Santander V, Monesterolo N, Casale C . Inhibition of flippase-like activity by tubulin regulates phosphatidylserine exposure in erythrocytes from hypertensive and diabetic patients. J Biochem. 2021; 169(6):731-745. DOI: 10.1093/jb/mvab016. View

Santander V, Bisig C, Purro S, Casale C, Arce C, Barra H . Tubulin must be acetylated in order to form a complex with membrane Na(+),K (+)-ATPase and to inhibit its enzyme activity. Mol Cell Biochem. 2006; 291(1-2):167-74. DOI: 10.1007/s11010-006-9212-9. View

10.

Mata A . Functional interplay between plasma membrane Ca-ATPase, amyloid β-peptide and tau. Neurosci Lett. 2017; 663:55-59. DOI: 10.1016/j.neulet.2017.08.004. View

11.

Berrocal M, Mata A . The Plasma Membrane Ca-ATPase, a Molecular Target for Tau-induced Cytosolic Calcium Dysregulation. Neuroscience. 2022; 518:112-118. DOI: 10.1016/j.neuroscience.2022.04.016. View

12.

Naffa R, Padanyi R, Ignacz A, Hegyi Z, Jezso B, Toth S . The Plasma Membrane Ca Pump PMCA4b Regulates Melanoma Cell Migration through Remodeling of the Actin Cytoskeleton. Cancers (Basel). 2021; 13(6). PMC: 8002435. DOI: 10.3390/cancers13061354. View

13.

Balach M, Santander V, Elisio E, Rivelli J, Muhlberger T, Campetelli A . Tubulin-mediated anatomical and functional changes caused by Ca in human erythrocytes. J Physiol Biochem. 2023; 79(3):511-527. DOI: 10.1007/s13105-023-00946-4. View

14.

Conrard L, Tyteca D . Regulation of Membrane Calcium Transport Proteins by the Surrounding Lipid Environment. Biomolecules. 2019; 9(10). PMC: 6843150. DOI: 10.3390/biom9100513. View

15.

Falchetto R, Vorherr T, Brunner J, Carafoli E . The plasma membrane Ca2+ pump contains a site that interacts with its calmodulin-binding domain. J Biol Chem. 1991; 266(5):2930-6. View

16.

Falchetto R, Vorherr T, Carafoli E . The calmodulin-binding site of the plasma membrane Ca2+ pump interacts with the transduction domain of the enzyme. Protein Sci. 1992; 1(12):1613-21. PMC: 2142131. DOI: 10.1002/pro.5560011209. View

17.

Yazawa M, Vorherr T, James P, Carafoli E, Yagi K . Binding of calcium by calmodulin: influence of the calmodulin binding domain of the plasma membrane calcium pump. Biochemistry. 1992; 31(12):3171-6. DOI: 10.1021/bi00127a018. View

18.

Tidow H, Poulsen L, Andreeva A, Knudsen M, Hein K, Wiuf C . A bimodular mechanism of calcium control in eukaryotes. Nature. 2012; 491(7424):468-72. DOI: 10.1038/nature11539. View

19.

Hofmann F, James P, Vorherr T, Carafoli E . The C-terminal domain of the plasma membrane Ca2+ pump contains three high affinity Ca2+ binding sites. J Biol Chem. 1993; 268(14):10252-9. View

20.

Niggli V, Adunyah E, Carafoli E . Acidic phospholipids, unsaturated fatty acids, and limited proteolysis mimic the effect of calmodulin on the purified erythrocyte Ca2+ - ATPase. J Biol Chem. 1981; 256(16):8588-92. View