Charbonnier F, Périn J P, Roussel G, Nussbaum J L, Alliel P M
Centre de Neurochimie du CNRS, Strasbourg.
C R Seances Soc Biol Fil. 1997;191(1):127-33.
We have recently cloned a novel proteoglycan initially identified in human testis and hence previously called testican. A close examination of the overall protein structure reveals three main regions: four osteonectin/SPARC-like domains encompassing the amino-terminal and central part of the deduced protein, a Kazal-like motif overlapping the third domain, and the CWCV domain in the carboxyl-terminal end region of the protein core. We propose to call it SPOCK, the acronym of SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan, according to its specific multidomain structure. To get further insight into the function, a Northern blot analysis was performed in order to determine the site of expression in various adult tissues; a 5.2 kb transcript appeared only but strongly in mouse brain. The structure of the murine brain proteoglycan was determined through molecular cloning; human and mouse deduced proteins are highly homologous with 95% overall amino acid identity. Murine brain serial sections hybridized with cDNA and immunological probes revealed identical distribution in discrete cerebral regions, such as CA3 hippocampal region and cerebellum. Immunoelectron microscopy showed the antigen selectively localized in the post-synaptic density of scattered pyramidal neurons and Purkinje cells. Structural analysis, a main expression in nervous system and preliminary assignment of the human gene in a critical region for neuropathologies, suggest that SPOCK may be of importance in neural development and neurodegenerative diseases.
我们最近克隆了一种新的蛋白聚糖,最初在人类睾丸中发现,因此以前称为睾丸蛋白聚糖。对其整体蛋白质结构的仔细研究揭示了三个主要区域:四个骨连接蛋白/富含半胱氨酸的酸性分泌蛋白(SPARC)样结构域,涵盖推导蛋白的氨基末端和中央部分;一个与第三个结构域重叠的Kazal样基序;以及位于蛋白核心羧基末端区域的CWCV结构域。根据其特定的多结构域结构,我们建议将其命名为SPOCK,即SPARC/骨连接蛋白CWCV和Kazal样结构域蛋白聚糖的首字母缩写。为了进一步深入了解其功能,进行了Northern印迹分析,以确定其在各种成年组织中的表达部位;一个5.2 kb的转录本仅在小鼠脑中强烈出现。通过分子克隆确定了小鼠脑蛋白聚糖的结构;人和小鼠的推导蛋白高度同源,总体氨基酸同一性为95%。用cDNA和免疫探针杂交的小鼠脑连续切片显示,在离散的脑区,如海马CA3区和小脑中分布相同。免疫电子显微镜显示,抗原选择性地定位于散在的锥体神经元和浦肯野细胞的突触后致密区。结构分析、在神经系统中的主要表达以及人类基因在神经病理学关键区域的初步定位表明,SPOCK可能在神经发育和神经退行性疾病中具有重要意义。