Deficiency of Sorting Nexin 27 (SNX27) Leads to Growth Retardation and Elevated Levels of N-Methyl-D-Aspartate Receptor 2C (NR2C)
Deficiency of Sorting Nexin 27 (SNX27) Leads to Growth Retardation and Elevated Levels of N-Methyl-D-Aspartate Receptor 2C (NR2C)
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DOI：
10.1128/mcb.01044-10
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发表时间：
2011-04-01
影响因子：
5.3
通讯作者：
Hong, Wanjin
中科院分区：
文献类型：
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作者：
Cai, Lei;Loo, Li Shen;Hong, Wanjin
包含 Phox (PX) 结构域的分选连接蛋白 (SNX) 正在成为内吞运输的重要调节因子。分选 nexin 27 (SNX27) 是独特的，因为它包含 PDZ (Psd-95/Dlg/ZO1) 结构域。我们在此表明，SNX27 主要通过其 PX 结构域与 PtdIns(3) P 相互作用而靶向早期内体。尽管小鼠中 SNX27 基因的靶向消融并未显着影响胚胎发育过程中的生长和存活，但 SNX27 在出生后生长和存活中发挥着重要作用。 N-甲基-D-天冬氨酸 (NMDA) 受体 2C (NR2C) 被鉴定为一种新型 SNX27 相互作用蛋白，这种相互作用是由 SNX27 的 PDZ 结构域和 NR2C 的 C 端 PDZ 结合基序介导的。 NR2C 表达水平增加以及 SNX27(-/-) 神经元中 NR2C 内吞作用受损，表明 SNX27 可能具有调节 NR2C 内吞作用和/或内体分选的功能。这与 SNX27 作为含有 PDZ 结合基序的膜蛋白分选的通用调节剂的作用一致，并且它的缺失可能会改变这些蛋白质的运输，导致生长和生存缺陷。
Phox (PX) domain-containing sorting nexins (SNXs) are emerging as important regulators of endocytic trafficking. Sorting nexin 27 (SNX27) is unique, as it contains a PDZ (Psd-95/Dlg/ZO1) domain. We show here that SNX27 is primarily targeted to the early endosome by interaction of its PX domain with PtdIns(3) P. Although targeted ablation of the SNX27 gene in mice did not significantly affect growth and survival during embryonic development, SNX27 plays an essential role in postnatal growth and survival. N-Methyl-D-aspartate (NMDA) receptor 2C (NR2C) was identified as a novel SNX27-interacting protein, and this interaction is mediated by the PDZ domain of SNX27 and the C-terminal PDZ-binding motif of NR2C. Increased NR2C expression levels, together with impaired NR2C endocytosis in SNX27(-/-) neurons, indicate that SNX27 may function to regulate endocytosis and/or endosomal sorting of NR2C. This is consistent with a role of SNX27 as a general regulator for sorting of membrane proteins containing a PDZ-binding motif, and its absence may alter the trafficking of these proteins, leading to growth and survival defects.