Braunewell Karl-Heinz, Klein-Szanto Andres J
Molecular and Cellular Neuroscience Laboratory, Department Biochemistry and Molecular Biology, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA.
Cell Tissue Res. 2009 Feb;335(2):301-16. doi: 10.1007/s00441-008-0716-3. Epub 2008 Nov 7.
The visinin-like protein (VSNL) subfamily, including VILIP-1 (the founder protein), VILIP-2, VILIP-3, hippocalcin, and neurocalcin delta, constitute a highly homologous subfamily of neuronal calcium sensor (NCS) proteins. Comparative studies have shown that VSNLs are expressed predominantly in the brain with restricted expression patterns in various subsets of neurons but are also found in peripheral organs. In addition, the proteins display differences in their calcium affinities, in their membrane-binding kinetics, and in the intracellular targets to which they associate after calcium binding. Even though the proteins use a similar calcium-myristoyl switch mechanism to translocate to cellular membranes, they show calcium-dependent localization to various subcellular compartments when expressed in the same neuron. These distinct calcium-myristoyl switch properties might be explained by specificity for defined phospholipids and membrane-bound targets; this enables VSNLs to modulate various cellular signal transduction pathways, including cyclic nucleotide and MAPK signaling. An emerging theme is the direct or indirect effect of VSNLs on gene expression and their interaction with components of membrane trafficking complexes, with a possible role in membrane trafficking of different receptors and ion channels, such as glutamate receptors of the kainate and AMPA subtype, nicotinic acetylcholine receptors, and Ca(2+)-channels. One hypothesis is that the highly homologous VSNLs have evolved to fulfil specialized functions in membrane trafficking and thereby affect neuronal signaling and differentiation in defined subsets of neurons. VSNLs are involved in differentiation processes showing a tumor-invasion-suppressor function in peripheral organs. Finally, VSNLs play neuroprotective and neurotoxic roles and have been implicated in neurodegenerative diseases.
类视锥蛋白（VSNL）亚家族，包括VILIP - 1（该家族的首个发现蛋白）、VILIP - 2、VILIP - 3、海马钙结合蛋白和神经钙蛋白δ，构成了神经元钙传感器（NCS）蛋白的一个高度同源亚家族。比较研究表明，VSNL主要在大脑中表达，在不同神经元亚群中具有受限的表达模式，但在外周器官中也有发现。此外，这些蛋白在钙亲和力、膜结合动力学以及钙结合后与之结合的细胞内靶点方面存在差异。尽管这些蛋白利用相似的钙 - 肉豆蔻酰开关机制转运至细胞膜，但当在同一神经元中表达时，它们在不同亚细胞区室中呈现钙依赖性定位。这些独特的钙 - 肉豆蔻酰开关特性可能由对特定磷脂和膜结合靶点的特异性来解释；这使得VSNL能够调节各种细胞信号转导途径，包括环核苷酸和MAPK信号通路。一个新出现的主题是VSNL对基因表达的直接或间接影响以及它们与膜转运复合物成分的相互作用，可能在不同受体和离子通道（如红藻氨酸和AMPA亚型的谷氨酸受体、烟碱型乙酰胆碱受体以及Ca(2 +)通道）的膜转运中发挥作用。一种假说认为，高度同源的VSNL已经进化以在膜转运中发挥特定功能，从而影响特定神经元亚群中的神经元信号传导和分化。VSNL参与分化过程，在外周器官中表现出肿瘤侵袭抑制功能。最后，VSNL发挥神经保护和神经毒性作用，并与神经退行性疾病有关。
