Testican-3: a brain-specific proteoglycan member of the BM-40/SPARC/osteonectin family

Testican-3: a brain-specific proteoglycan member of the BM-40/SPARC/osteonectin family
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DOI:
10.1111/jnc.12212
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发表时间:
2013-05-01
影响因子:
4.7
通讯作者:
Paulsson, Mats
Paulsson, Mats
中科院分区:
医学2区
文献类型:
--
作者:
Hartmann, Ursula;Huelsmann, Hanni;Paulsson, Mats

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睾丸是分泌蛋白聚糖的三成员家族,其结构与细胞外钙结合蛋白的 BM-40/酸性分泌蛋白和富含半胱氨酸 (SPARC) 骨连接蛋白家族相关。体外研究表明,睾丸参与细胞外蛋白酶级联和神经元功能的调节。在这里,我们描述了小鼠 testican-3 的生化特征和组织分布以及相应基因的失活。成年小鼠中 testican-3 的表达仅限于大脑,它广泛位于细胞外基质内,并与细胞相关。脑源性 testican-3 是一种硫酸乙酰肝素蛋白聚糖。在细胞培养中,核心蛋白在上清液和细胞外基质中检测到,而蛋白聚糖形式仅限于上清液。这表明 testican-3 核心蛋白与细胞外基质成分可能存在相互作用,而细胞外基质成分可通过添加糖胺聚糖链而被阻断。缺乏 testican-3 的小鼠能够存活并具有生育能力,并且没有表现出明显的表型。这表明睾丸家族不同成员之间或 testican-3 和其他大脑硫酸乙酰肝素蛋白聚糖之间存在功能冗余。
The testicans are a three-member family of secreted proteoglycans structurally related to the BM-40/secreted protein acidic and rich in cystein (SPARC) osteonectin family of extracellular calcium-binding proteins. In vitro studies have indicated that testicans are involved in the regulation of extracellular protease cascades and in neuronal function. Here, we describe the biochemical characterization and tissue distribution of mouse testican-3 as well as the inactivation of the corresponding gene. The expression of testican-3 in adult mice is restricted to the brain, where it is located diffusely within the extracellular matrix, as well as associated with cells. Brain-derived testican-3 is a heparan sulphate proteoglycan. In cell culture, the core protein is detected in the supernatant and the extracellular matrix, whereas the proteoglycan form is restricted to the supernatant. This indicates possible interactions of the testican-3 core protein with components of the extracellular matrix which are blocked by addition of the glycosaminoglycan chains. Mice deficient in testican-3 are viable and fertile and do not show an obvious phenotype. This points to a functional redundancy among the different members of the testican family or between testican-3 and other brain heparan sulphate proteoglycans.