Journal article
The use of transgenic mouse models to reveal the functions of Ca2+ buffer proteins in excitable cells.
- Schwaller B Unit of Anatomy, Department of Medicine, University of Fribourg, Fribourg, Switzerland. Beat.Schwaller@unifr.ch
- 2011-12-06
Published in:
- Biochimica et biophysica acta. - 2012
Animals
Calbindin 1
Calbindin 2
Calbindins
Calcium Signaling
Humans
Mice
Mice, Transgenic
Mitochondria, Muscle
Neurons
Parvalbumins
Phenotype
S100 Calcium Binding Protein G
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.bbagen.2011.11.008
- PMID 22138448
- Persistent URL
- https://sonar.ch/global/documents/138819
Statistics
Document views: 17
File downloads: