Making a little affinity go a long way: A topological view of LFA-1 regulation

Making a little affinity go a long way: A topological view of LFA-1 regulation
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DOI:
10.3109/15419069809004481
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发表时间:
1998-01-01
期刊:
CELL ADHESION AND COMMUNICATION
影响因子:
--
通讯作者:
Dustin, ML
Dustin, ML
中科院分区:
其他
文献类型:
--
作者:
Dustin, ML

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淋巴细胞利用粘附性在体内导航,并与各种潜在的抗原提呈细胞瞬间相互作用。黏附分子的相互作用受质量作用定律和相对生物膜的鲜为人知的规则所支配。生物化学参数,如黏附分子亲和力,只说明了部分情况。侧向移动性、膜排列和细胞骨架相互作用等因素在决定最终结果方面同样重要。因此,确定细胞膜和细胞骨架的性质增强或阻碍黏附分子相互作用的机制是重要的。我的实验室的工作表明,淋巴细胞黏附分子合作的一个机制是以纳米级的精度排列黏附膜。在这里,我讨论了一个依赖于三个独立过程的LFA-I调节模型:LFA-1横向迁移率,配体诱导的少量高亲和力LFA-1的产生和局部膜对齐。我认为,这些过程的协调可以使稳定的粘连和脱离之间的快速相互转化。
Lymphocytes utilize adhesion to navigate in the body and to transiently interact with a variety of potential antigen presenting cells. Interactions of adhesion molecules are governed by the law of mass action and the less understood rules of apposed biological membranes. Biochemical parameters such as adhesion molecule affinity only tell part of the story. Factors such as lateral mobility, membrane alignment and cytoskeletal interactions are equally important in determining the final outcome. Therefore it is important to determine mechanisms by which the properties of cell membranes and the cytoskeleton reinforce or hinder adhesion molecule interactions. Work from my lab has shown that one mechanism by which lymphocyte adhesion molecules cooperate is to align adhering membranes with nanometer precision. Here, I discuss a model for LFA-I regulation that is dependent on three independent processes: LFA-1 lateral mobility, ligand induced generation of a small amount of high affinity LFA-1 and local membrane alignment. I propose that coordination of these processes allows rapid interconversion between stable adhesion and detachment.