Cytosolic Ca Buffers Are Inherently Ca Signal Modulators

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2019 Jul 17

PMID 31308146

Citations 34

Authors

Beat Schwaller

Affiliations

Soon will be listed here.

Abstract

For precisely regulating intracellular Ca signals in a time- and space-dependent manner, cells make use of various components of the "Ca signaling toolkit," including Ca entry and Ca extrusion systems. A class of cytosolic Ca-binding proteins termed Ca buffers serves as modulators of such, mostly short-lived Ca signals. Prototypical Ca buffers include parvalbumins (α and β isoforms), calbindin-D9k, calbindin-D28k, and calretinin. Although initially considered to function as pure Ca buffers, that is, as intracellular Ca signal modulators controlling the shape (amplitude, decay, spread) of Ca signals, evidence has accumulated that calbindin-D28k and calretinin have additional Ca sensor functions. These other functions are brought about by direct interactions with target proteins, thereby modulating their targets' function/activity. Dysregulation of Ca buffer expression is associated with several neurologic/neurodevelopmental disorders including autism spectrum disorder (ASD) and schizophrenia. In some cases, the presence of these proteins is presumed to confer a neuroprotective effect, as evidenced in animal models of Parkinson's or Alzheimer's disease.

Citing Articles

The roles of mitochondria in global and local intracellular calcium signalling.

Cartes-Saavedra B, Ghosh A, Hajnoczky G Nat Rev Mol Cell Biol. 2025; .

PMID: 39870977 DOI: 10.1038/s41580-024-00820-1.

Can Magnoflorine Improve Memory? Immunohistochemical Studies on Parvalbumin Immunoreactive Neurons and Fibers of Mice Hippocampus.

Szalak R, Komar M, Kowalczuk-Vasilev E, Kruk-Slomka M, Zagorska J, Arciszewski M Nutrients. 2025; 17(1.

PMID: 39796570 PMC: 11722722. DOI: 10.3390/nu17010137.

Parvalbumin gates chronic pain through the modulation of firing patterns in inhibitory neurons.

Qiu H, Miraucourt L, Petitjean H, Xu M, Theriault C, Davidova A Proc Natl Acad Sci U S A. 2024; 121(27):e2403777121.

PMID: 38916998 PMC: 11228497. DOI: 10.1073/pnas.2403777121.

Cerebellum Purkinje cell vulnerability in aged rats with memory impairment.

Cooper C, Cheng L, Bhatti J, Rivera E, Huell D, Banuelos C J Comp Neurol. 2024; 532(4):e25610.

PMID: 38605461 PMC: 11027960. DOI: 10.1002/cne.25610.

Elevations in the Mitochondrial Matrix Protein Cyclophilin D Correlate With Reduced Parvalbumin Expression in the Prefrontal Cortex of Patients With Schizophrenia.

OBrien J, Jalilvand S, Suji N, Jupelly R, Phensy A, Mwirigi J Schizophr Bull. 2024; 50(5):1197-1207.

PMID: 38412332 PMC: 11349014. DOI: 10.1093/schbul/sbae016.

References

Westerink R, Beekwilder J, Wadman W . Differential alterations of synaptic plasticity in dentate gyrus and CA1 hippocampal area of Calbindin-D28K knockout mice. Brain Res. 2012; 1450:1-10. DOI: 10.1016/j.brainres.2012.02.036. View

Sotonyi P, Gao Q, Bechmann I, Horvath T . Estrogen promotes parvalbumin expression in arcuate nucleus POMC neurons. Reprod Sci. 2010; 17(12):1077-80. DOI: 10.1177/1933719110379651. View

Gotzos V, Vogt P, Celio M . The calcium binding protein calretinin is a selective marker for malignant pleural mesotheliomas of the epithelial type. Pathol Res Pract. 1996; 192(2):137-47. DOI: 10.1016/S0344-0338(96)80208-1. View

Bischop D, Orduz D, Lambot L, Schiffmann S, Gall D . Control of neuronal excitability by calcium binding proteins: a new mathematical model for striatal fast-spiking interneurons. Front Mol Neurosci. 2012; 5:78. PMC: 3392946. DOI: 10.3389/fnmol.2012.00078. View

Neher E . Usefulness and limitations of linear approximations to the understanding of Ca++ signals. Cell Calcium. 1999; 24(5-6):345-57. DOI: 10.1016/s0143-4160(98)90058-6. View

Wang C, Jiang C, Yuan H, Xiao C, Gao D . Role of calbindin-D28K in estrogen treatment for Parkinson's disease. Neural Regen Res. 2014; 8(8):702-7. PMC: 4146078. DOI: 10.3969/j.issn.1673-5374.2013.08.004. View

Alberi L, Lintas A, Kretz R, Schwaller B, Villa A . The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons. J Neurophysiol. 2013; 109(11):2827-41. DOI: 10.1152/jn.00375.2012. View

Bearzatto B, Servais L, Roussel C, Gall D, Baba-Aissa F, Schurmans S . Targeted calretinin expression in granule cells of calretinin-null mice restores normal cerebellar functions. FASEB J. 2005; 20(2):380-2. DOI: 10.1096/fj.05-3785fje. View

Eyles D, McGrath J, Reynolds G . Neuronal calcium-binding proteins and schizophrenia. Schizophr Res. 2002; 57(1):27-34. DOI: 10.1016/s0920-9964(01)00299-7. View

10.

Kojetin D, Venters R, Kordys D, Thompson R, Kumar R, Cavanagh J . Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K). Nat Struct Mol Biol. 2006; 13(7):641-7. DOI: 10.1038/nsmb1112. View

11.

Chen G, Racay P, Bichet S, Celio M, Eggli P, Schwaller B . Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells. Neuroscience. 2006; 142(1):97-105. DOI: 10.1016/j.neuroscience.2006.06.008. View

12.

Sun S, Li F, Gao X, Zhu Y, Chen J, Zhu X . Calbindin-D28K inhibits apoptosis in dopaminergic neurons by activation of the PI3-kinase-Akt signaling pathway. Neuroscience. 2011; 199:359-67. DOI: 10.1016/j.neuroscience.2011.09.054. View

13.

Veerasakul S, Watiktinkorn P, Thanoi S, Dalton C, Fachim H, Nudmamud-Thanoi S . Increased DNA methylation in the parvalbumin gene promoter is associated with methamphetamine dependence. Pharmacogenomics. 2017; 18(14):1317-1322. DOI: 10.2217/pgs-2016-0188. View

14.

Hu H, Gan J, Jonas P . Interneurons. Fast-spiking, parvalbumin⁺ GABAergic interneurons: from cellular design to microcircuit function. Science. 2014; 345(6196):1255263. DOI: 10.1126/science.1255263. View

15.

Kretsinger R, Nockolds C . Carp muscle calcium-binding protein. II. Structure determination and general description. J Biol Chem. 1973; 248(9):3313-26. View

16.

Lukas W, Jones K . Cortical neurons containing calretinin are selectively resistant to calcium overload and excitotoxicity in vitro. Neuroscience. 1994; 61(2):307-16. DOI: 10.1016/0306-4522(94)90233-x. View

17.

Leberer E, Pette D . Neural regulation of parvalbumin expression in mammalian skeletal muscle. Biochem J. 1986; 235(1):67-73. PMC: 1146649. DOI: 10.1042/bj2350067. View

18.

Ferguson B, Gao W . PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders. Front Neural Circuits. 2018; 12:37. PMC: 5964203. DOI: 10.3389/fncir.2018.00037. View

19.

Wohr M, Roullet F, Hung A, Sheng M, Crawley J . Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior. PLoS One. 2011; 6(6):e20631. PMC: 3111434. DOI: 10.1371/journal.pone.0020631. View

20.

Cheron G, Gall D, Servais L, Dan B, Maex R, Schiffmann S . Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice. J Neurosci. 2004; 24(2):434-41. PMC: 6730003. DOI: 10.1523/JNEUROSCI.3197-03.2004. View