Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs.

Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs.
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DOI:
10.3390/membranes5030253
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发表时间:
2015-07-03
期刊:
影响因子:
4.2
通讯作者:
Pandey KN
Pandey KN
中科院分区:
工程技术4区
文献类型:
--
作者:
Pandey KN

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跨膜受体的靶向内吞作用和跨膜受体在膜结合的亚细胞器中的重新分布对其正确的信号和生理功能至关重要。负责内化和转运途径的膜受体被分类成包被的囊泡。心脏激素、心钠素和脑利钠肽(ANP和BNP)与鸟苷酸环化酶/利钠肽受体A(GC-A/NPRA)结合,诱导细胞内第二信使环鸟苷3‘,5’-单磷酸(CGMP)的产生,从而降低血压和心力衰竭的发生率。在配体结合后,受体被迅速内化、隔离并重新分布到细胞内。因此,NPRA被认为是一种动态的细胞大分子,在其一生中遍历不同的亚细胞位置。药物和分子微扰剂的使用有助于描述完整细胞内吞、转运、下调和降解膜受体的途径。本文就NPRA的内化、转运和再分布机制与其他细胞表面受体从质膜到细胞内部的比较进行了综述。简要综述了不同的短信号肽序列基序在其他膜受体内化和转运中的作用,并讨论了它们在NPRA内化和转运中的潜在意义。
The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP) bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed.