Schwaller Beat, Meyer Michael, Schiffmann Serge
Institute of Histology and General Embryology, University of Fribourg, Fribourg, Switzerland.
Cerebellum. 2002 Dec;1(4):241-58. doi: 10.1080/147342202320883551.
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.
钙视网膜蛋白（CR）、钙结合蛋白D-28k（CB）和小白蛋白（PV）属于EF手型钙结合蛋白大家族，在人类中该家族包含200多个成员。从结构上看，这些蛋白质的特征是存在数量可变的进化上高度保守的螺旋-环-螺旋基序，这些基序能以高亲和力结合Ca2+离子。在功能上，它们分为两类：通过与靶蛋白相互作用，钙传感器将钙浓度转化为信号级联反应，而钙缓冲蛋白则被认为可改变钙瞬变的时空特征。尽管目前认为CR、CB和PV是钙缓冲蛋白，但随着我们对它们生物学特性的了解增多，这种情况可能会改变。它们生物物理特性的显著差异导致了快速和慢速缓冲蛋白的区分，并提示了单个钙缓冲蛋白的功能特异性。最近培育出的缺乏这些蛋白质的小鼠品系有助于评估CR、CB和PV的生理作用。在此，我们特别参照小脑来综述这些钙结合蛋白的生物学特性，因为它们在特定的小脑神经元中特别丰富。CR主要表达于颗粒细胞及其平行纤维，而PV和CB则存在于浦肯野细胞的整个轴突、胞体、树突和棘中。此外，在抑制性中间神经元的一个亚群，即星状细胞和篮状细胞中也发现了PV。对基因敲除小鼠的研究以及体外实验工作，再加上它们在小脑中独特的细胞类型特异性分布，表明这些钙结合蛋白已进化成为细胞内钙瞬变的功能不同、生理相关的调节剂。对不同脑区的分析表明，这些蛋白质参与调节对突触可塑性至关重要的钙库。令人惊讶的是，这三种钙结合蛋白中的任何一种作为内源性神经保护剂的主要作用通常并不成立。
