Mobilization of the endocytic membrane system by intracellular signalling

真核细胞，包括人类细胞，被分成称为细胞器的隔间，这些细胞器已经进化成执行特定功能的同时保护细胞的其余部分免受潜在有害活动的影响。这种不同细胞器的分离使细胞在协调细胞活动与细胞分裂以及与其周围环境的变化方面面临巨大挑战。这种协调需要存在专门的电路，将细胞外信号传递到细胞内细胞器。这些细胞内信号通路由蛋白质硬件组成，通过可逆的蛋白质修饰传递信号，包括蛋白质磷酸化。因此，蛋白激酶，即催化蛋白质磷酸化的酶，扮演着传递信号的分子开关的角色。我们对信号转导机制的了解大多局限于细胞质膜上最初的信号接收和整合。然而，类似的信号装置存在于细胞器的细胞膜上，特别是那些通过基于囊泡的膜交通(内小体)参与膜和大分子的调节运输的信号装置，但它们在膜交通协调中的作用尚不清楚。这项研究计划试图了解人类细胞如何协调细胞膜运输，以应对细胞需求和适应周围环境的变化。我们将研究存在于称为核周循环隔室的特殊隔室中的关键酪氨酸激酶。它们在调节膜交通方面的作用将在基本的细胞过程中得到解决，这些过程需要将膜成分有规律地输送到细胞的特定区域，包括细胞分裂。这项拟议的研究旨在了解细胞生物学中一个基本的悬而未决的问题，该问题与人类疾病有潜在的联系，其特征是细胞无法对外部信号做出适当的反应，包括增殖性和退行性疾病。

Eukaryotic cells, including human cells, are divided into compartments called organelles that have evolved to perform specialized functions while protecting the rest of the cell from potentially harmful activities. This partition into distinct organelles presents cells with big challenges in terms of coordination of cellular activities with cell division and with changes in their surrounding environment. Such coordination requires the presence of specialized circuits that relay extracellular signals to intracellular organelles. These intracellular signaling circuits are composed of protein hardware that conveys signals through reversible protein modifications, including protein phosphorylation. Hence, protein kinases, the enzymes that catalyze protein phosphorylation, act as molecular switches to transduce signals. Most of our knowledge regarding signaling mechanisms is limited to the initial signal reception and integration at the plasma membrane. However, similar signaling devices reside on intracellular membranes of organelles, notably those involved in the regulated transport of membranes and macromolecules via vesicle-based membrane traffic (endosomes), but their role in coordination of membrane traffic is not understood. This research program seeks to understand how human cells coordinate membrane traffic in order to cope with cellular needs and adjust to changes in their surrounding. We will investigate key tyrosine kinases residing within a specialized compartment called the perinuclear recycling compartment. Their role in regulation of membrane traffic will be addressed during fundamental cellular processes requiring the regulated delivery of membrane components to specific regions of the cell, including cell division. The proposed research aims at understanding a basic unresolved issue in cell biology with potential links to human diseases characterized by an inability of cells to properly respond to external cues, including proliferative and degenerative diseases.