Deciphering the role of secretory pathways in the reciprocal connection between the cellular nutrient sensing machinery and the extracellular matrix

破译分泌途径在细胞营养传感机制和细胞外基质之间相互连接中的作用

• 批准号: 505661449
• 负责人: Dr. Constantinos Demetriades, Ph.D.
• 金额: --
• 依托单位: Max-Planck-Institut für Biologie des Alterns
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/505661449?language=en
• 关键词: Deciphering; role; secretory; pathways; reciprocal

Cells interact with their environment in a reciprocal manner via surface or secreted proteins. On the one hand, stimuli from the cellular milieu regulate the activity of signalling pathways, and thereby, influence the cellular physiology . On the other hand, cells respond to intra- and extracellular cues by modifying the set of proteins that are actively transported to their surface or secreted into the extracellular space. These include the extracellular matrix (ECM), integrins, receptors, transporters, cytokines and other proteins that mediate key cellular functions such as signalling, intercellular communication, adhesion, chemotaxis, motility and survival. Therefore, inside-out and outside-in processes are part of a functional network that controls cellular homeostasis in health and disease. Here, we aim to investigate the fundamental molecular mechanisms that govern the intricate interplay between nutrient/mTORC1 signalling, cellular metabolism, cargo selection, protein secretion and the ECM. Moreover, in close collaboration with other partners in the consortium, we will study the role of these crucial cellular processes in musculoskeletal homeostasis and disease using relevant cell line models. Collectively, our work will likely have direct translational implications by revealing potential targets for drug development against rheumatoid arthritis, muscle cachexia and other human diseases that manifest with muscle, skeletal, dental or cartilage anomalies.

细胞通过表面或分泌的蛋白质以互惠的方式与环境相互作用。一方面，来自细胞环境的刺激调节信号通路的活动，从而影响细胞生理。另一方面，细胞对细胞内和细胞外的信号作出反应，通过修饰一组蛋白质，这些蛋白质被主动运送到细胞表面或分泌到细胞外空间。这些包括细胞外基质（ECM）、整合素、受体、转运体、细胞因子和其他介导关键细胞功能的蛋白质，如信号传导、细胞间通讯、粘附、趋化、运动和生存。因此，由内到外和由外到内的过程是控制健康和疾病中细胞稳态的功能网络的一部分。在这里，我们的目标是研究控制营养/mTORC1信号传导、细胞代谢、货物选择、蛋白质分泌和ECM之间复杂相互作用的基本分子机制。此外，在与联盟其他伙伴的密切合作下，我们将使用相关细胞系模型研究这些关键细胞过程在肌肉骨骼稳态和疾病中的作用。总的来说，我们的工作很可能通过揭示药物开发的潜在靶点来直接转化类风湿关节炎、肌肉恶病质和其他以肌肉、骨骼、牙齿或软骨异常为表现的人类疾病。