Characterization of cell type-specific endocannabinoid signaling at biochemical and behavioral level

生化和行为水平上细胞类型特异性内源性大麻素信号传导的表征

• 批准号: 62829775
• 负责人: Professor Dr. Beat Lutz
• 金额: --
• 依托单位: Institut für Physiologische Chemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/62829775?language=en
• 关键词: Characterization; cell; type; specific; endocannabinoid

Multi-protein complexes can constitute regulatory signaling units, which are able to integrate and modify a multitude of different signals received by the cell from extracellular and/or intracellular sources. Proteins with high numbers of functional connections are called “hub proteins” and are particularly interesting as central regulators and integrators of cellular processes, including synaptic plasticity, cell division, and cell differentiation. The endocannabinoid system (ECS) represents a widespread signaling system, both in the nervous system, but also in non-neuronal cell types. In this proposal, we aim at identifying multi-protein complexes formed by the CB1 receptor. We will employ the so-called tandem affinity purification (TAP) method, allowing the isolation of native protein complexes with subsequent protein sequence determination by MALDI-TOF. In extension to previous work, we aim at allocating CB1 receptor functions to the serotonergic system, combining behavioral, electrophysiological and the biochemical methods. By comparing CB1 receptor function in three different neurotransmitter systems (glutamatergic, GABAergic, serotonergic system), these experiments should shed novel light onto cell type-specific CB1 receptor signaling processes.

多蛋白复合物可以构成调节信号传导单元，其能够整合和修饰细胞从细胞外和/或细胞内来源接收的多种不同信号。具有大量功能连接的蛋白质被称为“枢纽蛋白”，作为细胞过程（包括突触可塑性、细胞分裂和细胞分化）的中央调节剂和整合剂而特别令人感兴趣。内源性大麻素系统（ECS）代表了一种广泛的信号系统，不仅在神经系统中，而且在非神经元细胞类型中。在本提案中，我们的目标是鉴定由 CB1 受体形成的多蛋白复合物。我们将采用所谓的串联亲和纯化 (TAP) 方法，允许分离天然蛋白质复合物，并随后通过 MALDI-TOF 确定蛋白质序列。在之前工作的基础上，我们的目标是结合行为学、电生理学和生化方法，将 CB1 受体功能分配给血清素能系统。通过比较三种不同神经递质系统（谷氨酸能、GABA能、血清素能系统）中的 CB1 受体功能，这些实验应该为细胞类型特异性 CB1 受体信号传导过程提供新的线索。

项目成果

Neuron‐type specific cannabinoid‐mediated G protein signalling in mouse hippocampus

小鼠海马神经元类型特异性大麻素介导的 G 蛋白信号传导

• DOI: 10.1111/jnc.12137
• 发表时间: 2013
• 期刊: Journal of Neurochemistry
• 影响因子: 4.7
• 作者: Steindel F;Lerner R;Häring M;Ruehle S;Marsicano G;Lutz B;Monory K
• 通讯作者: Monory K

Age differences in the role of the cannabinoid type 1 receptor on glutamatergic neurons in habituation and spatial memory acquisition.

大麻素 1 型受体对谷氨酸能神经元在习惯化和空间记忆获取中的作用的年龄差异

• DOI: 10.1016/j.lfs.2015.01.034
• 发表时间: 2015
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Legler A;Monory K;Lutz B
• 通讯作者: Lutz B

Cell Type-Specific Tandem Affinity Purification of the Mouse Hippocampal CB1 Receptor-Associated Proteome.

小鼠海马 CB1 受体相关蛋白质组的细胞类型特异性串联亲和纯化

• DOI: 10.1021/acs.jproteome.6b00339
• 发表时间: 2016
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Mattheus T;Kukla K;Zimmermann T;Tenzer S;Lutz B
• 通讯作者: Lutz B

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging

• DOI: 10.1073/pnas.1016442108
• 发表时间: 2011-07-05
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Albayram, Onder;Alferink, Judith;Bilkei-Gorzo, Andras
• 通讯作者: Bilkei-Gorzo, Andras

Cannabinoid 1 Receptors in Keratinocytes Modulate Proinflammatory Chemokine Secretion and Attenuate Contact Allergic Inflammation

• DOI: 10.4049/jimmunol.1201777
• 发表时间: 2013-05-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Gaffal, Evelyn;Cron, Mira;Tueting, Thomas
• 通讯作者: Tueting, Thomas