Molecular analysis of CD44 in cell adhesion and migration

CD44在细胞粘附和迁移中的分子分析

• 批准号: 105429-2011
• 负责人: Johnson, Pauline
• 金额: $ 2.91万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506158
• 关键词: Molecular; analysis; CD44; cell; adhesion

CD44 is a cell adhesion molecule expressed on many cells in your body. We are interested in its function on white blood cells, the cells of the immune system that fight infection and disease. The CD44 molecule helps white blood cells arrive at the site of infection, helps resolve inflammation and heal wounds, and is also involved in the migration of tumor cells resulting in tumor metastasis. It is our hypothesis that CD44 interacts with its binding partner, hyaluronan (HA) a sugar molecule that can attach to the cell wall. This interaction regulates immune cell function by aiding cell movement throughout the body. One set of immune cells, called T cells, circulate throughout the body looking for invaders that cause infection. Once they find them, they stop, receive signals from other cells to become armed, then migrate through the blood to infected tissues to fight infection. Knowing when to migrate and when to stop is critical to their function. In this study we will determine how the interaction of CD44 with HA influences T cell adhesion and mobility. When CD44 attaches to HA, signals are transmitted to a network of proteins inside the cell that change the cell's shape and cause mobility. Changes to this network are required each time the cell moves, thus signals that change this network can affect cell mobility. We have found that CD44 signals via an enzyme (catalyst) that is associated with CD44 inside the cell. We are now looking for substrates (targets) of this enzyme to follow the signaling pathway directly to the network using immunochemistry and biochemical techniques. We have found that HA signals through CD44 to destabilize the cell structure, thus allowing the network to remodel and the cell to change its shape. This basic research into what makes a cell stop or migrate is of fundamental importance in cell biology. Understanding at the molecular level what regulates immune cell adhesion and migration is an important step towards the future development of new biotechnologies designed to facilitate, mimic or prevent cell movement or cell adhesion. By investing in this basic research, Canadians are ensuring the continuation of scientific discovery and progress for future generations.

CD44是一种细胞粘附分子，在人体内的许多细胞上都有表达。我们感兴趣的是它对白细胞的作用，白细胞是免疫系统中对抗感染和疾病的细胞。CD44分子帮助白细胞到达感染部位，帮助消除炎症和愈合伤口，也参与肿瘤细胞的迁移导致肿瘤转移。我们的假设是CD44与其结合伙伴透明质酸（HA）相互作用，透明质酸是一种可以附着在细胞壁上的糖分子。这种相互作用通过帮助细胞在全身运动来调节免疫细胞的功能。一组被称为T细胞的免疫细胞在体内循环，寻找引起感染的入侵者。一旦它们找到它们，它们就会停下来，接收来自其他细胞的信号，武装起来，然后通过血液迁移到受感染的组织，对抗感染。知道何时迁移和何时停止对它们的功能至关重要。在这项研究中，我们将确定CD44与HA的相互作用如何影响T细胞的粘附和移动性。当CD44附着在HA上时，信号被传递到细胞内的蛋白质网络，从而改变细胞的形状并引起细胞的移动。每次细胞移动时都需要改变这个网络，因此改变这个网络的信号会影响细胞的移动。我们发现CD44通过细胞内与CD44相关的酶（催化剂）发出信号。我们现在正在利用免疫化学和生化技术寻找这种酶的底物（靶点），以遵循信号通路直接进入网络。我们发现，HA通过CD44信号破坏细胞结构的稳定性，从而允许网络重塑和细胞改变其形状。这项关于细胞停止或迁移的原因的基础研究在细胞生物学中具有重要的基础意义。在分子水平上理解是什么调节了免疫细胞的粘附和迁移，是未来发展新的生物技术的重要一步，这些技术旨在促进、模拟或防止细胞运动或细胞粘附。通过对这一基础研究的投资，加拿大人正在为子孙后代确保科学发现和进步的继续。