LFA-1 and ICAM-1 mediate a bi-directional signaling across the cell membrane which is essential for biological functions of lymphocyte, including exudation, activation, adhesion, immunosurveillance as well as immuno-logical synapse formation. The signal transducing is a dynamic process and dependent on the binding capacity between LFA-1 and ICAM-1. The affinity and the avidity of LFA-1 are two major regulation forms in this process. Phosphorylation of LFA-1 and cytoskeleton protein talin 1 play a critical role in signal transducing. In biology of lymphocyte, LFA-1 and ICAM-1 interaction forms the co-stimulatory signal to promote activation, proliferation and division. In this article the regulation of binding capacity between LFA-1 and ICAM-1, the regulation of LFA-1 subunit phosphorylation, the role of talin1 in signaling transduction of LFA-1 and ICAM-1, the synergic stimulatory signaling of LPA-1 and ICAM-1 were reviewed.
Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; physiology ; Ligands ; Lymphocyte Function-Associated Antigen-1 ; metabolism ; physiology ; Lymphocytes ; cytology ; immunology ; metabolism ; Phosphorylation ; Signal Transduction ; physiology ; Talin ; metabolism

OBJECTIVE: To investigate the expression of Talin1 in the fallopian tube and chorionic villi in patients with tubal pregnancy and its role in regulating invasion and migration of trophoblasts. METHODS: Immunohistochemistry and Western blotting were used to detect the localization and expression level of Talin1 in the fallopian tube and chorionic villi in patients with tubal pregnancy and in women with normal pregnancy. In the cell experiment, HTR-8/SVneo cells was transfected with Talin1 siRNA and the changes in cell invasion and migration were assessed using scratch assay and Transwell assay. The expressions of MMP-2, MMP-9, N-cadherin and Snail in the transfected cells were detected by qRT-PCR and Western blotting. RESULTS: Positive expression of Talin1 was detected in both normal fallopian tube tissues and tissues from women tubal pregnancy, and its expression was localized mainly in the cytoplasm of cilia cells. The expression level of Talin1 was significantly higher in both the fallopian tube and chorionic villi in women with tubal pregnancy than in normal fallopian tube and chorionic villi samples (P < 0.01). In HTR-8/SVneo cells, transfection with Talin1 siRNA significantly inhibited cell invasion (P < 0.01) and migration (P < 0.05), down-regulated the expression of N-cadherin, MMP-2 and Snail (P < 0.05), and up-regulated the expression of MMP-9 in the cells (P < 0.05). CONCLUSION The expression of Talin1 in the fallopian tube and chorionic villi is significantly increased in women with tubal pregnancy, suggesting the association of Talin1-regulated trophoblast cell invasion with the occurrence of tubal pregnancy.
Cadherins/metabolism* ; Cell Movement ; Chorionic Villi/metabolism* ; Fallopian Tubes/metabolism* ; Female ; Humans ; Matrix Metalloproteinase 2/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Pregnancy ; Pregnancy, Tubal/metabolism* ; RNA, Small Interfering/metabolism* ; Talin/metabolism* ; Trophoblasts/metabolism*

Tumor angiogenesis induced by vascular endothelial cells (VECs) migration is a necessary condition for tumor growth and metastasis. The purpose of this study is to investigate the effect of focal adhesion kinase (FAK) inhibitor (50nmol/mL) on the adhesion and migration of endothelial cells(ECs) and the expression of focal adhesion proteins vinculin, talin and paxillin. Scratch wound migration assay was performed to examine the effect of FAK inhibitor with 50nmol/mL on ECs migration at 0, 5, 10, 30, 60 and 120min, respectively. And immunofluorescence analysis was performed to detect the expression of F-actin in ECs treated with FAK inhibitor within 2h. Western blot was carried out to determine the effect of FAK inhibitor on expression of vinculin, talin and paxillin proteins. The results showed that the migration distance and the expression of F-actin in ECs treated with FAK inhibitor decreased significantly compared with that of the controls, and the level of vinculin showed no significant difference with increasing of treated time of FAK inhibitor. However, the talin and paxillin showed an identical decreasing tendency in 5-10min, but slowly going up in 30min and then after subsequently decreasing. The results of this study proved that blocking phosphorylation of FAK could inhibit VECs adhesion and migration by downregulating focal adhesion proteins so that it may inhibit tumor angiogenesis. This may provide a new approach for tumor therapy.
Cell Adhesion ; Cell Movement ; physiology ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Focal Adhesion Protein-Tyrosine Kinases ; antagonists & inhibitors ; metabolism ; Focal Adhesions ; metabolism ; physiology ; Humans ; Neoplasms ; blood supply ; Neovascularization, Pathologic ; Paxillin ; metabolism ; Talin ; metabolism ; Vinculin ; metabolism

Integrins are allosteric cell adhesion receptors that cycle from a low to a high affinity ligand binding state, a complex process of receptor activation that is of particular importance in blood cells such as platelets or leukocytes. Here we highlight recent progress in the understanding of the molecular pathways that regulate integrin activation in platelets and leukocytes, with a special focus on the structural changes in platelet integrin αIIbβ3 brought about by key intracellular proteins, namely talin and kindlins, that are of crucial importance in the regulation of integrin function. Evidence that the small GTPase Rap1 and its guanine exchange factor CalDAG-GEF1, together with RIAM, a Rap1GTP adaptor protein, promote the interaction of talin with the integrin β subunit, has greatly contributed to fill the gap in our understanding of the signaling pathway from G-coupled agonist receptors and their phospholipase C-dependant second messengers, to integrin activation. Studies of patients with the rare blood cell disorder LAD-III have contributed to the identification of kindlins as new co-regulators of the talin-dependent integrin activation process in platelets and leukocytes, underlining the relevance for the in-depth investigation of patients with rare genetic blood cell disorders.
Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cell Adhesion ; Cytoskeleton ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Platelet Glycoprotein GPIIb-IIIa Complex ; metabolism ; Protein Interaction Domains and Motifs ; Recombinant Proteins ; metabolism ; Sequence Alignment ; Talin ; metabolism