Integrin Activation

2001 ◽  
Vol 86 (07) ◽  
pp. 316-323 ◽  
Author(s):  
D. G. Woodside ◽  
S. Liu ◽  
M. H. Ginsberg
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Ligand Binding ◽  
Cellular Adhesion ◽  
Structural Basis ◽  
Surface Adhesion ◽  
Integrin Activation ◽  
Ligand Activation ◽  
Dependent Cell

SummaryIntegrins are cell surface adhesion receptors that participate in a variety of important processes throughout the vasculature. Here we summarize some recent findings on the regulation of integrin mediated cellular adhesion. Particular emphasis is placed on the regulation of integrin affinity for ligand (activation), although this is just one mechanism by which regulation of integrin-dependent cell adhesion can occur. Also discussed are recent observations on the structural basis of integrin activation, the role of the cytoplasmic domain in integrin affinity regulation, and potential mechanisms by which activation signals are propagated from integrin cytoplasmic domains to the extracellular ligand binding domain.

scholarly journals Integrin activation takes shape

2002 ◽  
Vol 158 (5) ◽  
pp. 833-839 ◽  
Author(s):  
R.C. Liddington ◽  
M.H. Ginsberg
Keyword(s):  
Cell Surface ◽  
Ligand Binding ◽  
Cytoplasmic Domain ◽  
Structural Basis ◽  
Surface Adhesion ◽  
Integrin Activation ◽  
Adhesion Receptors ◽  
Ligand Activation ◽  
And Function

Integrins are cell surface adhesion receptors that are essential for the development and function of multicellular animals. Here we summarize recent findings on the regulation of integrin affinity for ligand (activation), one mechanism by which cells modulate integrin function. The focus is on the structural basis of integrin activation, the role of the cytoplasmic domain in integrin affinity regulation, and potential mechanisms by which activation signals are propagated from integrin cytoplasmic domains to the extracellular ligand-binding domain.

scholarly journals Dual role of the actin cytoskeleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1.

1997 ◽  
Vol 8 (2) ◽  
pp. 341-351 ◽  
Author(s):  
M Lub ◽  
Y van Kooyk ◽  
S J van Vliet ◽  
C G Figdor
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Ligand Binding ◽  
Actin Cytoskeleton ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocyte Function ◽  
Intracellular Signals ◽  
Cytoskeletal Elements

Intracellular signals are required to activate the leukocyte-specific adhesion receptor lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) to bind its ligand, intracellular adhesion molecule-1 (ICAM-1). In this study, we investigated the role of the cytoskeleton in LFA-1 activation and demonstrate that filamentous actin (F-actin) can both enhance and inhibit LFA-1-mediated adhesion, depending on the distribution of LFA-1 on the cell surface. We observed that LFA-1 is already clustered on the cell surface of interleukin-2/phytohemagglutinin-activated lymphocytes. These cells bind strongly ICAM-1 and disruption of the actin cytoskeleton inhibits adhesion. In contrast to interleukin-2/phytohemagglutinin-activated peripheral blood lymphocytes, resting lymphocytes, which display a homogenous cell surface distribution of LFA-1, respond poorly to intracellular signals to bind ICAM-1, unless the actin cytoskeleton is disrupted. On resting peripheral blood lymphocytes, uncoupling of LFA-1 from the actin cytoskeleton induces clustering of LFA-1 and this, along with induction of a high-affinity form of LFA-1, via "inside-out" signaling, results in enhanced binding to ICAM-1, which is dependent on intact intermediate filaments, microtubules, and metabolic energy. We hypothesize that linkage of LFA-1 to cytoskeletal elements prevents movement of LFA-1 over the cell surface, thus inhibiting clustering and strong ligand binding. Release from these cytoskeletal elements allows lateral movement and activation of LFA-1, resulting in ligand binding and "outside-in" signaling, that subsequently stimulates actin polymerization and stabilizes cell adhesion.

scholarly journals Extracellular Ca2+ modulates leukocyte function-associated antigen-1 cell surface distribution on T lymphocytes and consequently affects cell adhesion

1994 ◽  
Vol 124 (6) ◽  
pp. 1061-1070 ◽  
Author(s):  
Y van Kooyk ◽  
P Weder ◽  
K Heije ◽  
CG Figdor
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Ligand Binding ◽  
Surface Distribution ◽  
Ligand Interaction ◽  
Weak Binding ◽  
Leukocyte Function ◽  
Distinct Site

Transition of leukocyte function-associated antigen-1 (LFA-1), from an inactive into an activate state depends on the presence of extracellular Mg2+ and/or Ca2+ ions. Although Mg2+ is directly involved in ligand binding, the role of Ca2+ in LFA-1 mediated adhesion remained obscure. We now demonstrate that binding of Ca2+, but not Mg2+, directly correlates with clustering of LFA-1 molecules at the cell surface of T cells, thereby facilitating LFA-1-ligand interaction. Using a reporter antibody (NKI-L16) that recognizes a Ca(2+)-dependent epitope on LFA-1, we found that Ca2+ can be bound by LFA-1 with different strength. We noticed that weak binding of Ca2+ is associated with a dispersed LFA-1 surface distribution on T cells and with non-responsiveness of these cells to stimuli known to activate LFA-1. In contrast, stable binding of Ca2+ by LFA-1 correlates with a patch-like surface distribution and vivid ligand binding after activation of LFA-1. Mg(2+)-dependent ligand binding does not affect binding of Ca2+ by LFA-1 as measured by NKI-L16 expression, suggesting that Mg2+ binds to a distinct site, and that both cations are important to mediate adhesion. Only Sr2+ ions can replace Ca2+ to express the L16 epitope, and to induce clustering of LFA-1 at the cell surface. We conclude that Ca2+ is involved in avidity regulation of LFA-1 by clustering of LFA-1 molecules at the cell surface, whereas Mg2+ is important in regulation of the affinity of LFA-1 for its ligands.

The role of cadherins and catenins in gliomagenesis

2006 ◽  
Vol 21 (4) ◽  
pp. 1-4 ◽  
Author(s):  
Kaveh Barami ◽  
Laura Lewis-Tuffin ◽  
Panos Z. Anastasiadis
Keyword(s):  
Cell Adhesion ◽  
Normal Tissue ◽  
Cell Of Origin ◽  
Surface Adhesion ◽  
Therapeutic Approaches ◽  
Calcium Dependent ◽  
New Therapeutic Approaches ◽  
Dependent Cell ◽  
Cell Cell

✓Cell–cell adhesion is a crucial process occurring during normal tissue development. Cadherins are calcium-dependent cell-surface adhesion molecules involved in cell–cell adhesion. They reorganize the actin cytoskeleton via interaction with the catenins. Modulation of the cadherin/catenin system plays a role in cell motility. Dysregulation of the cadherin/catenin assembly has been implicated in various cancers. In this review, the authors summarize all studies focusing on the role of cadherins and catenins in glioma formation. With the emergence of recent data regarding gliomas' putative cell of origin, elucidation of the role of cadherins/catenins in gliomagenesis will become important in devising new therapeutic approaches against such deadly cancers.

scholarly journals Glioma Pathogenesis-Related 1-Like 1 Is Testis Enriched, Dynamically Modified, and Redistributed during Male Germ Cell Maturation and Has a Potential Role in Sperm-Oocyte Binding

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2331-2342 ◽  
Author(s):  
Gerard M. Gibbs ◽  
Jennifer Chi Yi Lo ◽  
Brett Nixon ◽  
Duangporn Jamsai ◽  
Anne E. O'Connor ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Zona Pellucida ◽  
Secretory Protein ◽  
Cellular Adhesion ◽  
Binding Assays ◽  
Distinct Subgroup ◽  
Functional Studies ◽  
Pathogenesis Related ◽  
Antigen 5

The glioma pathogenesis-related 1 (GLIPR1) family consists of three genes [GLIPR1, GLIPR1-like 1 (GLIPR1L1), and GLIPR1-like 2 (GLIPR1L2)] and forms a distinct subgroup within the cysteine-rich secretory protein (CRISP), antigen 5, and pathogenesis-related 1 (CAP) superfamily. CAP superfamily proteins are found in phyla ranging from plants to humans and, based largely on expression and limited functional studies, are hypothesized to have roles in carcinogenesis, immunity, cell adhesion, and male fertility. Specifically data from a number of systems suggests that sequences within the C-terminal CAP domain of CAP proteins have the ability to promote cell-cell adhesion. Herein we cloned mouse Glipr1l1 and have shown it has a testis-enriched expression profile. GLIPR1L1 is posttranslationally modified by N-linked glycosylation during spermatogenesis and ultimately becomes localized to the connecting piece of elongated spermatids and sperm. After sperm capacitation, however, GLIPR1L1 is also localized to the anterior regions of the sperm head. Zona pellucida binding assays indicate that GLIPR1L1 has a role in the binding of sperm to the zona pellucida surrounding the oocyte. These data suggest that, along with other members of the CAP superfamily and several other proteins, GLIPR1L1 is involved in the binding of sperm to the oocyte complex. Collectively these data further strengthen the role of CAP domain-containing proteins in cellular adhesion and propose a mechanism whereby CAP proteins show overlapping functional significance during fertilization.

Role of LFA-1/ICAM-1-dependent cell adhesion in CD40-mediated inhibition of anti-IgM antibody-induced B-cell death

1995 ◽  
Vol 96 (6) ◽  
pp. 1136-1144 ◽  
Author(s):  
M MAYUMI ◽  
S SUMIMOTO ◽  
Y OHSHIMA ◽  
K KATAMURA ◽  
T HEIKE ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Adhesion ◽  
B Cell ◽  
Igm Antibody ◽  
Dependent Cell

Effect of colcemid on the locomotory behaviour of fibroblasts

Development ◽  
1970 ◽  
Vol 24 (3) ◽  
pp. 625-640
Author(s):  
Ju. M. Vasiliev ◽  
I. M. Gelfand ◽  
L. V. Domnina ◽  
O. Y. Ivanova ◽  
S. G. Komm ◽  
...  
Keyword(s):  
Cell Surface ◽  
Electron Microscopic Examination ◽  
Mouse Fibroblast ◽  
Active State ◽  
Structural Basis ◽  
Fish Scale ◽  
Electron Microscopic ◽  
Locomotory Behaviour ◽  
Embryonic Fibroblast

Effects of metaphase inhibitors (colcemid, colchicine, vinblastine) on mouse and human embryonic, fibroblast-like cells growing on glass and on an oriented substrate (fish scale) were studied. All three inhibitors caused similar changes in the form of interphase cells and inhibited their directional locomotion. The effects of two inhibitors (colcemid and vinblastine) were found to be completely reversible. Microcinematographic studies have shown that the most conspicuous change of locomotory behaviour induced by colcemid was the disappearance of non-active stable parts of the cell edge; in normal cells only the leading part of the edge was actively moving, while in colcemid-treated cells all parts of the edge eventually became active. Activation of the whole edge made these cells unable to perform directional translocation. It is suggested that colcemid and other metaphase inhibitors prevent stabilization of the non-active state of the cell surface. The possible role of this suggested colcemid-sensitive stabilization mechanism in the normal locomotory behaviour of fibroblasts is discussed. Electron-microscopic examination has shown that microtubules disappeared from the cytoplasm of colcemid-treated, mouse, fibroblast-like cells. The formation of microtubules as the possible structural basis of the stabilization of the non-active state of the cell surface is discussed.

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