生物
细胞生物学
整合素
内体
跨膜蛋白
酪氨酸
磷酸化
信号转导衔接蛋白
SH2域
蛋白质酪氨酸磷酸酶
原癌基因酪氨酸蛋白激酶Src
受体酪氨酸激酶
膜蛋白
内吞作用
信号转导
作者
M. Fabbri,L. Fumagalli,G. Bossi,Elisabetta Bianchi,Jeffrey R. Bender,Ruggero Pardi
标识
DOI:10.1093/emboj/18.18.4915
摘要
Integrins play pivotal roles in supporting shear- and mechanical-stress-resistant cell adhesion and migration. These functions require the integrity of the short beta subunit cytoplasmic domains, which contain multiple, highly conserved tyrosine-based endocytic signals, typically found in receptors undergoing regulated, clathrin-dependent endocytosis. We hypothesized that these sequences may control surface integrin dynamics in statically adherent and/or locomoting cells via regulated internalization and polarized recycling of the receptors. By using site-directed mutagenesis and ectopic expression of the alphaL/beta2 integrin in Chinese hamster ovary cells, we found that Y735 in the membrane-proximal YRRF sequence is selectively required for recycling of spontaneously internalized receptors to the cell surface and to growth factor-induced membrane ruffles. Disruption of this motif by non-conservative substitutions has no effect on the receptor's adhesive function, but diverts internalized integrins from a recycling compartment into a degradative pathway. Conversely, the non-conservative F754A substitution in the membrane-proximal NPLF sequence abrogates ligand-dependent adhesion and spreading without affecting receptor recycling. Both of these mutants display a severe impairment in ligand-supported migration, suggesting the existence in integrin cytoplasmic domains of independent signals regulating apparently unrelated functions that are required to sustain cell migration over specific ligands.
科研通智能强力驱动
Strongly Powered by AbleSci AI