Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes.
Synaptopodin: an actin-associated protein in telencephalic dendrites and renal podocytes.
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DOI：
10.1083/jcb.139.1.193
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发表时间：
1997-10-06
期刊：
影响因子：
--
通讯作者：
Kriz W
中科院分区：
文献类型：
--
作者：
Mundel P;Heid HW;Mundel TM;Krüger M;Reiser J;Kriz W
突触足蛋白是分化足细胞的肌动蛋白相关蛋白，其也作为突触后致密物（PSD）的肌动蛋白细胞骨架的一部分和仅端脑突触的亚群中的相关树突棘出现。在纯化的大鼠肾脏和前脑突触足蛋白中测定的氨基酸序列以及来自人和小鼠脑cDNA克隆的氨基酸序列与任何已知蛋白质均无显着同源性。特别是，synaptopodin不包含在受体聚集PSD蛋白中发现的功能结构域。突触足蛋白的开放阅读框编码一种多肽，其计算的Mr为73.7 kD（人）/74.0 kD（小鼠），等电点为9.38（人）/9.27（小鼠）。突触足蛋白含有大量的脯氨酸（约20%），沿蛋白质均匀分布沿着，因此实际上排除了任何球状结构域的形成。人类和小鼠突触足蛋白之间的序列比较显示在蛋白质水平上84%的同一性。在体内和体外的脑和肾中，突触足蛋白基因的表达是分化依赖性的。在大鼠脑的出生后成熟过程中，突触足蛋白首先在第15天通过蛋白质印迹分析检测到，并且在成年动物中达到最大表达。端脑中唯一的突触足蛋白合成已经通过原位杂交证实，其中突触足蛋白mRNA仅在嗅球、大脑皮层、纹状体和海马的胞体中发现，即，该表达仅限于高突触可塑性的区域。从这些结果和培养细胞的实验，我们得出结论，synaptopodin代表一种新的富含脯氨酸，肌动蛋白相关蛋白，可能发挥作用，在调制肌动蛋白为基础的形状和运动的树突棘和足细胞足突。
Synaptopodin is an actin-associated protein of differentiated podocytes that also occurs as part of the actin cytoskeleton of postsynaptic densities (PSD) and associated dendritic spines in a subpopulation of exclusively telencephalic synapses. Amino acid sequences determined in purified rat kidney and forebrain synaptopodin and derived from human and mouse brain cDNA clones show no significant homology to any known protein. In particular, synaptopodin does not contain functional domains found in receptor-clustering PSD proteins. The open reading frame of synaptopodin encodes a polypeptide with a calculated Mr of 73.7 kD (human)/74.0 kD (mouse) and an isoelectric point of 9.38 (human)/9.27 (mouse). Synaptopodin contains a high amount of proline (∼20%) equally distributed along the protein, thus virtually excluding the formation of any globular domain. Sequence comparison between human and mouse synaptopodin revealed 84% identity at the protein level. In both brain and kidney, in vivo and in vitro, synaptopodin gene expression is differentiation dependent. During postnatal maturation of rat brain, synaptopodin is first detected by Western blot analysis at day 15 and reaches maximum expression in the adult animal. The exclusive synaptopodin synthesis in the telencephalon has been confirmed by in situ hybridization, where synaptopodin mRNA is only found in perikarya of the olfactory bulb, cerebral cortex, striatum, and hippocampus, i.e., the expression is restricted to areas of high synaptic plasticity. From these results and experiments with cultured cells we conclude that synaptopodin represents a novel kind of proline-rich, actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and podocyte foot processes.