Beat Schwaller1. 1. Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland. Beat.Schwaller@unifr.ch
Abstract
BACKGROUND: Cytosolic Ca2+ buffers are members of the large family of Ca2+-binding proteins and are essential components of the Ca2+ signaling toolkit implicated in the precise regulation of intracellular Ca2+ signals. Their physiological role in excitable cells has been investigated in vivo by analyzing the phenotype of mice either lacking one of the Ca2+ buffers or mice with ectopic expression. SCOPE OF REVIEW: In this review, results obtained with knockout mice for the three most prominent Ca2+ buffers, parvalbumin, calbindin-D28k and calretinin are summarized. MAJOR CONCLUSIONS: The absence of Ca2+ buffers in specific neuron subpopulations, and for parvalbumin additionally in fast-twitch muscles, leads to Ca2+ buffer-specific changes in intracellular Ca2+ signals. This affects the excitation-contraction cycle in parvalbumin-deficient muscles, and in Ca2+ buffer-deficient neurons, properties associated with synaptic transmission (e.g. short-term modulation), excitability and network oscillations are altered. These findings have not only resulted in a better understanding of the physiological function of Ca2+ buffers, but have revealed that the absence of Ca2+ signaling toolkit components leads to protein-and neuron-specific adaptive/homeostatic changes that also include changes in neuron morphology (e.g. altered spine morphology, changes in mitochondria content) and network properties. GENERAL SIGNIFICANCE: The complex phenotype of Ca2+ buffer knockout mice arises from the direct effect of these proteins on Ca2+ signaling and moreover from the homeostatic mechanisms induced in these mice. For a better mechanistic understanding of neurological diseases linked to disturbed/altered Ca2+ signaling, a global view on Ca2+ signaling is expected to lead to new avenues for specific therapies. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.
BACKGROUND: Cytosolic Ca2+ buffers are members of the large family of Ca2+-binding proteins and are essential components of the Ca2+ signaling toolkit implicated in the precise regulation of intracellular Ca2+ signals. Their physiological role in excitable cells has been investigated in vivo by analyzing the phenotype of mice either lacking one of the Ca2+ buffers or mice with ectopic expression. SCOPE OF REVIEW: In this review, results obtained with knockout mice for the three most prominent Ca2+ buffers, parvalbumin, calbindin-D28k and calretinin are summarized. MAJOR CONCLUSIONS: The absence of Ca2+ buffers in specific neuron subpopulations, and for parvalbumin additionally in fast-twitch muscles, leads to Ca2+ buffer-specific changes in intracellular Ca2+ signals. This affects the excitation-contraction cycle in parvalbumin-deficient muscles, and in Ca2+ buffer-deficient neurons, properties associated with synaptic transmission (e.g. short-term modulation), excitability and network oscillations are altered. These findings have not only resulted in a better understanding of the physiological function of Ca2+ buffers, but have revealed that the absence of Ca2+ signaling toolkit components leads to protein-and neuron-specific adaptive/homeostatic changes that also include changes in neuron morphology (e.g. altered spine morphology, changes in mitochondria content) and network properties. GENERAL SIGNIFICANCE: The complex phenotype of Ca2+ buffer knockout mice arises from the direct effect of these proteins on Ca2+ signaling and moreover from the homeostatic mechanisms induced in these mice. For a better mechanistic understanding of neurological diseases linked to disturbed/altered Ca2+ signaling, a global view on Ca2+ signaling is expected to lead to new avenues for specific therapies. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.
Authors: Petr M Masliukov; Konstantin Moiseev; Antonina F Budnik; Alexandr D Nozdrachev; Jean-Pierre Timmermans Journal: Cell Mol Neurobiol Date: 2016-12-22 Impact factor: 5.046
Authors: Benton Tong; Aubrey J Hornak; Stéphane F Maison; Kevin K Ohlemiller; M Charles Liberman; Dwayne D Simmons Journal: J Neurosci Date: 2016-02-03 Impact factor: 6.167