Molecular analysis of CD44 in cell adhesion and migration

CD44是一种细胞黏附分子，表达在人体内的许多细胞上。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，帮助消炎和愈合伤口，还参与了导致肿瘤转移的肿瘤细胞的迁移。我们的假设是CD44与它的结合伙伴透明质酸(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的运动来调节免疫细胞的功能。一组名为T细胞的免疫细胞在全身循环，寻找导致感染的入侵者。一旦找到它们，它们就会停下来，接收其他细胞发出的信号，让它们武装起来，然后通过血液迁移到受感染的组织，以对抗感染。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细胞的黏附和移动。当CD44附着在HA上时，信号被传输到细胞内的蛋白质网络，从而改变细胞的形状并导致移动性。每次小区移动时都需要更改此网络，因此更改此网络的信号可能会影响小区的移动性。我们已经发现，CD44通过细胞内与CD44相关的一种酶(催化剂)发出信号。我们现在正在寻找这种酶的底物(靶标)，以利用免疫化学和生化技术沿着信号通路直接到达网络。我们发现HA通过CD44发出信号来破坏细胞结构的稳定，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基础研究在细胞生物学中具有重要意义。在分子水平上了解是什么调节了免疫细胞的黏附和迁移，这是朝着未来开发旨在促进、模拟或防止细胞移动或细胞黏附的新生物技术的重要一步。通过投资于这项基础研究，加拿大人正在确保科学发现和进步为子孙后代继续下去。

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.