The calcium sensing receptor life cycle: Trafficking, cell surface expression, and degradation
The calcium sensing receptor life cycle: Trafficking, cell surface expression, and degradation
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DOI：
10.1016/j.beem.2013.03.003
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发表时间：
2013-06-01
影响因子：
7.4
通讯作者：
Breitwieser, Gerda E.
中科院分区：
文献类型：
--
作者：
Breitwieser, Gerda E.
钙敏感受体（CaSR）必须在激动剂长期存在的情况下发挥作用，最近的研究表明，它在这种条件下发出信号的能力取决于调节其细胞运输的独特机制：本章将重点介绍支持细胞内内质网定位的CaSR池的证据，该池可以通过CaSR信号传导被动员到质膜，导致激动剂驱动的插入信号传导（ADIS）。我总结了小GTP结合蛋白（Rabs，Sar 1和ARF），货物受体或伴侣（p24 A，RAMPs）和相互作用的蛋白质（14-3-3蛋白，钙调素）在顺行运输CaSR的作用的证据，并讨论了潜在的信号专业化所产生的CaSR与小窝蛋白或细丝蛋白A/Rho的相互作用。最后，我总结了目前的知识CaSR内吞和降解的蛋白酶体和溶酶体，并强调最近的研究表明，有缺陷的CaSR或相互作用的蛋白突变体的贩运有助于病理钙稳态紊乱。(C)2013爱思唯尔有限公司版权所有。
The calcium-sensing receptor (CaSR) must function in the chronic presence of agonist, and recent studies suggest that its ability to signal under such conditions depends upon the unique mechanism(s) regulating its cellular trafficking: This chapter will highlight the evidence supporting an intracellular endoplasmic reticulum-localized pool of CaSR that can be mobilized to the plasma membrane by CaSR signaling, leading to agonist-driven insertional signaling (ADIS). I summarize evidence for the role of small GTP binding proteins (Rabs, Sar1 and ARFs), cargo receptors or chaperones (p24A, RAMPs) and interacting proteins (14-3-3 proteins, calmodulin) in anterograde trafficking of CaSR, and discuss the potential signaling specializations arising from CaSR interactions with caveolins or Filamin A/Rho. Finally, I summarize current knowledge about CaSR endocytosis and degradation by both the proteasome and lysosome, and highlight recent studies indicating that defective trafficking of CaSR or interacting protein mutants contributes to pathology in disorders of calcium homeostasis. (C) 2013 Elsevier Ltd. All rights reserved.