Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK/LIN-2 during rat brain development
Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK/LIN-2 during rat brain development
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DOI：
10.1523/jneurosci.19-17-07415.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Sheng, M
中科院分区：
文献类型：
--
作者：
Hsueh, YP;Sheng, M
细胞表面硫酸乙酰肝素蛋白聚糖的多配体家族通过其细胞质 C 末端尾部与 CASK/LIN-2（一种膜相关鸟苷酸激酶同源物）的 PDZ 结构域相互作用。 Syndecan-CASK 相互作用可能涉及细胞间信号传导和/或细胞粘附。在这里，我们通过原位杂交表明，syndecan-1至syndecan-4在成年大鼠脑中具有独特的mRNA分布，其中syndecan-2和-3是前脑神经元中表达的主要syndecan。在蛋白质水平上，syndecan-2 和 -3 在神经元内的定位存在差异； syndecan-3 集中在轴突中，而 syndecan-2 则集中在突触中。 syndecan-2 的突触积累发生在突触发育后期。 CASK 是多配体的细胞质结合伴侣，其亚细胞分布在发育过程中发生显着变化，从出生后前 2 周的主要轴突分布转变为成人大脑中的体细胞树突分布。 CASK分布的这种变化在时间和空间上与syndecan-3和-2的表达模式相关，这与这两种syndecan在体内与CASK的关联一致。为了支持这一点，我们能够从大脑提取物中共免疫沉淀 CASK 和 syndecan-3 的复合物。我们的结果表明，特定的多配体在大脑的各种细胞类型中差异表达，并针对神经元中不同的亚细胞区室，在那里它们可以发挥专门的功能。此外，在整个出生后发育过程中，CASK 得到适当表达和定位，以与神经元不同区室中的 syndecan-2 和 -3 相互作用。
The syndecan family of cell surface heparan sulfate proteoglycans interacts via their cytoplasmic C-terminal tail with the PDZ domain of CASK/LIN-2, a membrane-associated guanylate kinase homolog. The syndecan-CASK interaction may be involved in intercellular signaling and/or cell adhesion. Here we show that syndecan-1 to syndecan-4 have distinctive mRNA distributions in adult rat brain by in situ hybridization, with syndecan-2 and -3 being the major syndecans expressed in neurons of the forebrain. At the protein level, syndecan-2 and -3 are differentially localized within neurons; syndecan-3 is concentrated in axons, whereas syndecan-2 is localized in synapses. The synaptic accumulation of syndecan-2 occurs late in synapse development. CASK is a cytoplasmic-binding partner for syndecans, and its subcellular distribution changes strikingly during development, shifting from a primarily axonal distribution in the first 2 postnatal weeks to a somatodendritic distribution in adult brain. This change in CASK distribution correlates temporally and spatially with the expression patterns of syndecan-3 and -2, consistent with the association of both of these syndecans with CASK in vivo. In support of this, we were able to coimmunoprecipitate a complex of CASK and syndecan-3 from brain extracts. Our results indicate that specific syndecans are differentially expressed in various cell types of the brain and are targeted to distinct subcellular compartments in neurons, where they may serve specialized functions. Moreover, CASK is appropriately expressed and localized to interact with both syndecan-2 and -3 in different compartments of the neuron throughout postnatal development.