The role of the Dlg family in T cell polarisation

Dlg 家族在 T 细胞极化中的作用

• 批准号: nhmrc : 251619
• 负责人: Prof Sarah Russell
• 金额: $ 14.7万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-dlg-family-cell-polarisation/94598
• 关键词: role; Dlg; family; cell; polarisation

Immune defence against pathogens is primarily achieved by the activities of a range of blood cells, including T cells. T cells have specialised functions involving direct killing of the pathogen, and recruitment and activation of other immune cells. Many of these functions require the lymphocyte to become polarised, or asymmetric, in order to concentrate the appropriate cellular machinery towards the site of activity. Examples of polarisation in lymphocytes includes (i) the formation of a single protrusion, or uropod, that forms the basis for cell-cell interactions, (ii) the formation of an immune synapse which allows a T cell to recognise a pathogen, and (iii) the direction of the cellular killing machinery towards the target. The process of cell polarisation is best characterised in neurons and epithelial cells, both of which are asymmetric. In each cell type, a major mechanism of regulating polarisation is the expression and targeting of a family of proteins containing regions called PDZ domains. PDZ domains mediate protein-protein interactions and so allow the assembly of large molecular scaffolds which hold proteins in specific cell sites. The loss of cell polarity in some cells is thought to cause uncontrolled proliferation and tumour progression, and some of the PDZ-containing proteins are tumour suppressors. We have identified a PDZ-containing protein that is polarised in T cells, and have evidence that this protein interacts with and controls the polarisation of a cell surface receptor whose functions include the regulation of T cell function and proliferation. The aim of this proposal is to determine the mechanisms and functional consequences of polarisation of these two proteins in T cells, and to determine whether their interaction or polarisation is important for T cell proliferation.

对病原体的免疫防御主要是通过包括T细胞在内的一系列血细胞的活性来实现的。 T细胞具有涉及病原体直接杀死以及其他免疫细胞的募集和激活的专业功能。这些功能中的许多功能都要求淋巴细胞变得极化或不对称，以便将适当的细胞机械集中到活动部位。淋巴细胞中极化的实例包括（i）形成单个突起或乌拉托德，这是细胞 - 细胞相互作用的基础的形成，（ii）形成免疫突触，使T细胞识别病原体，以及（iii）细胞杀死靶向靶标的方向。细胞极化的过程最能表征在神经元和上皮细胞中，这两者都是不对称的。在每种细胞类型中，调节极化的主要机制是含有称为PDZ结构域的蛋白质家族的表达和靶向。 PDZ结构域介导蛋白质 - 蛋白质相互作用，因此允许组装大分子支架，这些支架在特定细胞部位中固定蛋白质。某些细胞中细胞极性的丧失被认为会导致不受控制的增殖和肿瘤进展，而某些含PDZ的蛋白质是肿瘤抑制剂。我们已经确定了一种在T细胞中极化的含PDZ的蛋白质，并有证据表明该蛋白与细胞表面受体的极化相互作用，其功能包括调节T细胞功能和增殖。该建议的目的是确定T细胞中这两种蛋白质极化的机理和功能后果，并确定它们的相互作用或极化对于T细胞增殖是否重要。