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

细胞通过表面或分泌的蛋白质以相互的方式与其环境相互作用。一方面，来自细胞环境的刺激调节信号通路的活性，从而影响细胞生理学。另一方面，细胞通过修饰主动转运到其表面或分泌到细胞外空间的蛋白质组来响应细胞内和细胞外信号。这些包括细胞外基质（ECM）、整联蛋白、受体、转运蛋白、细胞因子和介导关键细胞功能如信号传导、细胞间通讯、粘附、趋化性、运动性和存活的其他蛋白质。因此，由内向外和由外向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，我们的目标是调查的基本分子机制，管理营养/mTORC 1信号，细胞代谢，货物选择，蛋白质分泌和ECM之间的复杂的相互作用。此外，我们将与联盟中的其他合作伙伴密切合作，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，我们的工作可能会通过揭示针对类风湿性关节炎，肌肉恶病质和其他表现为肌肉，骨骼，牙齿或软骨异常的人类疾病的药物开发的潜在靶点而产生直接的翻译影响。

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.