小柯机器人

德国Max Delbrück亥姆霍兹协会分子医学中心Andreas Bock、Martin J. Lohse等研究人员合作发现，受体相关的独立cAMP纳米域介导GPCR信号的时空特异性。这一研究成果与2022年3月15日在线发表在国际学术期刊《细胞》上。

研究人员证明单个G蛋白偶联受体（GPCR）通过受体相关的独立cAMP纳米域（RAIN）发出信号，构成自给自足、独立的细胞信号单元。低浓度的胰高血糖素样肽1（GLP-1）和异丙肾上腺素分别在GLP-1和β2肾上腺素受体周围产生高度局部化的cAMP池，这些cAMP受到来自其他受体和细胞区室的保护。研究人员利用工程化的GPCR纳米管绘制了局部cAMP浓度图，揭示了仅几十纳米的梯度，并确定了单个RAIN的大小。许多这样的RAIN共存，使得一个细胞可以同时操作数以千计的独立细胞信号，而不是作为一个简单的"开/关"发挥作用。

据悉，GPCR将细胞外刺激转变成特定的细胞功能。细胞表达许多不同的GPCR，但所有这些GPCR只对少数第二信使发出信号，如cAMP。细胞如何区分由不同GPCR触发的信号以协调其复杂的功能在很大程度上是未知的。

附：英文原文

Title: Receptor-associated independent cAMP nanodomains mediate spatiotemporal specificity of GPCR signaling

Author: Selma E. Anton, Charlotte Kayser, Isabella Maiellaro, Katarina Nemec, Jan Mller, Andreas Koschinski, Manuela Zaccolo, Paolo Annibale, Martin Falcke, Martin J. Lohse, Andreas Bock

Issue&Volume: 2022-03-15

Abstract: G protein-coupled receptors (GPCRs) relay extracellular stimuli into specific cellularfunctions. Cells express many different GPCRs, but all these GPCRs signal to onlya few second messengers such as cAMP. It is largely unknown how cells distinguishbetween signals triggered by different GPCRs to orchestrate their complex functions.Here, we demonstrate that individual GPCRs signal via receptor-associated independentcAMP nanodomains (RAINs) that constitute self-sufficient, independent cell signalingunits. Low concentrations of glucagon-like peptide 1 (GLP-1) and isoproterenol exclusivelygenerate highly localized cAMP pools around GLP-1- and β2-adrenergic receptors, respectively, which are protected from cAMP originating from otherreceptors and cell compartments. Mapping local cAMP concentrations with engineeredGPCR nanorulers reveals gradients over only tens of nanometers that define the size of individualRAINs. The coexistence of many such RAINs allows a single cell to operate thousandsof independent cellular signals simultaneously, rather than function as a simple “on/off”switch.

DOI: 10.1016/j.cell.2022.02.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00191-X