'New' functions for 'old' proteins: The role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice

被引:316
作者
Schwaller B. [1 ,5 ]
Meyer M. [2 ,3 ]
Schiffmann S. [4 ]
机构
[1] Institute of Histology and General Embryology, University of Fribourg, Fribourg
[2] Max-Planck-Institute of Neurobiology, Department of Neurobiochemistry, Martinsried
[3] Institute of Ophthalmology, University College London, London
[4] Department of Neuroscience, Universite Libre de Bruxelles, School of Medicine, Brussels
[5] Institute of Histology and General Embryology, University of Fribourg, Perolles
关键词
Ataxia; Calcium-binding protein; Knockout mice; Purkinje cells; Synaptic plasticity;
D O I
10.1080/147342202320883551
中图分类号
学科分类号
摘要
Calretinin (CR), calbindin D-28k (CB) and parvalbumin (PV) belong to the large family of EF-hand calcium-binding proteins, which comprises more than 200 members in man. Structurally these proteins are characterized by the presence of a variable number of evolutionary well-conserved helix-loop-helix motives, which bind Ca2+ ions with high affinity. Functionally, they fall into two groups: by interaction with target proteins, calcium sensors translate calcium concentrations into signaling cascades, whereas calcium buffers are thought to modify the spatiotemporal aspects of calcium transients. Although CR, CB and PV are currently being considered calcium buffers, this may change as we learn more about their biology. Remarkable differences in their biophysical properties have led to the distinction of fast and slow buffers and suggested functional specificity of individual calcium buffers. Evaluation of the physiological roles of CR, CB and PV has been facilitated by the recent generation of mouse strains deficient in these proteins. Here, we review the biology of these calcium-binding proteins with distinct reference to the cerebellum, since they are particularly enriched in specific cerebellar neurons. CR is principally expressed in granule cells and their parallel fibres, while PV and CB are present throughout the axon, soma, dendrites and spines of Purkinje cells. PV is additionally found in a subpopulation of inhibitory interneurons, the stellate and basket cells. Studies on deficient mice together with in vitro work and their unique cell type-specific distribution in the cerebellum suggest that these calcium-binding proteins have evolved as functionally distinct, physiologically relevant modulators of intracellular calcium transients. Analysis of different brain regions suggests that these proteins are involved in regulating calcium pools critical for synaptic plasticity. Surprisingly, a major role of any of these three calcium-binding proteins as an endogenous neuroprotectant is not generally supported. © 2002 Martin Dunitz Ltd.
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页码:241 / 258
页数:17
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