Delta/Notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like ReDeat-cont ining protein T ryeted to dendrites of developing and adult central nervous system neurons

Delta/Notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like ReDeat-cont ining protein T ryeted to dendrites of developing and adult central nervous system neurons
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DOI:
10.1074/jbc.m110793200
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发表时间:
2002-07-12
影响因子:
4.8
通讯作者:
Kengaku, M
Kengaku, M
中科院分区:
生物学2区
文献类型:
--
作者:
Eiraku, M;Hirata, Y;Kengaku, M

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我们已经确定了一种新的含有表皮生长因子(EGF)样重复序列的单程跨膜蛋白,该蛋白在发育和成熟的中枢神经系统中特异表达。序列分析表明,胞外区的10个EGF样重复序列与发育重要的受体Notch及其配体Delta的EGF样重复序列密切相关。因此,我们将分子命名为Delta/Notch-like EGF相关受体(DNER)。DNER蛋白在几种类型的有丝分裂后神经元中都有强烈的表达,包括皮质和海马锥体神经元、小脑颗粒细胞和浦肯野细胞。DNER蛋白定位于树突质膜和内小体,并被排除在轴突之外,即使在过度表达时也是如此。DNER的树突状靶向需要胞质区域中基于酪氨酸的分选基序。DNER与外壳相关蛋白复合体AP-1在体内的直接结合强烈表明,DNER经历了AP-1依赖的分选,从跨高尔基网络到躯体树突间隔,然后通过内体系统。
We have identified a novel epidermal growth factor (EGF)-like repeat-containing single-pass transmembrane protein that is specifically expressed in the developing and mature central nervous system. Sequence analysis revealed that the 10 EGF-like repeats in the extracellular domain are closely related to those of the developmentally important receptor Notch and its ligand Delta. We thus named the molecule Delta/Notch-like EGF-related receptor (DNER). DNER protein is strongly expressed in several types of post-mitotic neurons, including cortical and hippocampal pyramidal neurons, cerebellar granule cells, and Purkinje cells. DNER protein is localized to the dendritic plasma membrane and endosomes and is excluded from the axons, even when overexpressed. The tyrosine-based sorting motif in the cytoplasmic domain is required for dendritic targeting of DNER. Direct in vivo binding of DNER to the coat-associated protein complex AP-1 strongly suggests that DNER undergoes AP-1-dependent sorting to the somatodendritic compartments from the transGolgi network and subsequent passage through the endosomal system.