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鸟苷酸环化酶/心钠素受体-A的内化与隔离动力学

Dynamics of internalization and sequestration of guanylyl cyclase/atrial natriuretic peptide receptor-A.

作者信息

Pandey K N

机构信息

Department of Physiology, Tulane University School of Medicine Health Sciences Center, New Orleans, LA 70112, USA.

出版信息

Can J Physiol Pharmacol. 2001 Aug;79(8):631-9.

Abstract

The guanylyl cyclase/natriuretic peptide receptor-A (NPRA), also referred to as GC-A, is a single polypeptide molecule. In its mature form, NPRA resides in the plasma membrane and consists of an extracellular ligand-binding domain, a single transmembrane-spanning region, and intracellular cytoplasmic domain that contains a protein kinase-like homology domain (KHD) and a guanylyl cyclase (GC) catalytic active site. The binding of atrial natriuretic peptide (ANP) to NPRA occurs at the plasma membrane; the receptor is synthesized on the polyribosomes of the endoplasmic reticulum, and is presumably degraded within the lysosomes. It is apparent that NPRA is a dynamic cellular macromolecule that traverses through different compartments of the cell through its lifetime. This review describes the experiments addressing the interaction of ANP with the NPRA, the receptor-mediated internalization and stoichiometric distribution of ANP-NPRA complexes from cell surface to cell interior, and its release into culture media. It is hypothesized that after internalization, the ligand-receptor complexes dissociate inside the cell and a population of NPRA recycles back to plasma membrane. Subsequently, some of the dissociated ligand molecules escape the lysosomal degradative pathway and are released intact into culture media, which reenter the cell by retroendocytotic mechanisms. By utilizing the pharmacologic and physiologic perturbants, the emphasis has been placed on the cellular regulation and processing of ligand-receptor complexes in intact cells. I conclude the discussion by examining the data available on the utilization of deletion mutations of NPRA cDNA, which has afforded experimental insights into the mechanisms the cell utilizes in modulating the expression and functioning of NPRA.

摘要

鸟苷酸环化酶/利钠肽受体-A(NPRA),也称为GC-A,是一种单一的多肽分子。NPRA的成熟形式位于质膜中,由细胞外配体结合结构域、单个跨膜区域和细胞内细胞质结构域组成,该细胞质结构域包含一个蛋白激酶样同源结构域(KHD)和一个鸟苷酸环化酶(GC)催化活性位点。心房利钠肽(ANP)与NPRA的结合发生在质膜上;该受体在内质网的多核糖体上合成,并可能在溶酶体内降解。显然,NPRA是一种动态的细胞大分子,在其生命周期中穿过细胞的不同区室。本综述描述了有关ANP与NPRA相互作用、受体介导的内化以及ANP-NPRA复合物从细胞表面到细胞内部的化学计量分布及其释放到培养基中的实验。据推测,内化后,配体-受体复合物在细胞内解离,一部分NPRA循环回到质膜。随后,一些解离的配体分子逃脱溶酶体降解途径并完整释放到培养基中,通过逆向胞吞机制重新进入细胞。通过利用药理学和生理学干扰因素,重点研究了完整细胞中配体-受体复合物的细胞调节和加工过程。我通过研究有关NPRA cDNA缺失突变利用情况的现有数据来结束讨论,这些数据为细胞调节NPRA表达和功能的机制提供了实验见解。

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