Dystroglycan: a multifunctional adaptor protein

2005 ◽  
Vol 33 (6) ◽  
pp. 1254-1255 ◽  
Author(s):  
J.R. Higginson ◽  
S.J. Winder
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cell Signalling ◽  
Adaptor Protein ◽  
Interacting Proteins ◽  
Cytoskeleton Reorganization ◽  
Membrane Spanning ◽  
New Research

Dystroglycan, a ubiquitous membrane-spanning cell adhesion molecule, is a crucial link between the actin cytoskeleton and the extracellular matrix. With a wide expression pattern and multiple interacting proteins, not only is dystroglycan now thought to be important as a structural molecule but also new research has suggested that it has a role in cell signalling, cytoskeleton reorganization and as a potential tumour suppressor.

scholarly journals Platelet/Endothelial Cell Adhesion Molecule-1 Serves as a Costimulatory Agonist Receptor That Modulates Integrin-Dependent Adhesion and Aggregation of Human Platelets

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 500-507 ◽  
Author(s):  
David Varon ◽  
Denise E. Jackson ◽  
Boris Shenkman ◽  
Rima Dardik ◽  
Ilya Tamarin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Human Platelets ◽  
Endothelial Cell Adhesion Molecule ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion

Abstract Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kD member of the Ig gene superfamily that is expressed on the surface of circulating platelets, monocytes, neutrophils, and selective T-cell subsets. It is also a major component of the endothelial cell intercellular junction. Previous studies have shown that cross-linking PECAM-1 on the surface of leukocytes results in the activation of adhesion molecules of both the β1 and β2integrin family. In addition, the process of leukocyte transendothelial migration appears to be mediated, at least in part, by homophilic adhesive interactions that take place between leukocyte and endothelial cell junctional PECAM-1 molecules. However, little is known about the functional role of this membrane glycoprotein in human platelets. In the present study, we examined the effects of PECAM-1 engagement on integrin-mediated platelet-extracellular matrix or platelet-platelet interactions. Bivalent, but not monovalent, anti–PECAM-1 monoclonal antibodies (MoAbs) specific for membrane-proximal Ig-homology domain 6 significantly augmented platelet deposition (increased surface coverage) and aggregation (increased average size) onto extracellular matrix, under both oscillatory or defined low shear flow conditions (200 s−1) in a modified cone and plate viscometer. Moreover, bivalent anti-domain 6 MoAbs were capable of serving as costimulatory agonists to markedly enhance both adenosine diphosphate (ADP)- and platelet activating factor (PAF)-induced platelet aggregation responses. These antibodies appeared to act via outside-in signal transduction through PECAM-1, as evidenced by the fact that their binding (1) led to conformational changes in the αIIbβ3 integrin complex, (2) induced surface expression of P-selectin, and (3) resulted in the tyrosine phosphorylation of PECAM-1. Together, these data support a role for PECAM-1 in cellular activation and suggest that PECAM-1 may serve as a costimulatory agonist receptor capable of modulating integrin function in human platelets during adhesion and aggregation.

Identification of Extracellular Matrix and Cell Adhesion Molecule Genes Associated with Muscle Development in Pigs

2011 ◽  
Vol 30 (7) ◽  
pp. 469-479 ◽  
Author(s):  
Xishan Ma ◽  
Zhonglin Tang ◽  
Ning Wang ◽  
Shuanping Zhao ◽  
Ruiqi Wang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Muscle Development

scholarly journals Platelet/Endothelial Cell Adhesion Molecule-1 Serves as a Costimulatory Agonist Receptor That Modulates Integrin-Dependent Adhesion and Aggregation of Human Platelets

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 500-507 ◽  
Author(s):  
David Varon ◽  
Denise E. Jackson ◽  
Boris Shenkman ◽  
Rima Dardik ◽  
Ilya Tamarin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Human Platelets ◽  
Endothelial Cell Adhesion Molecule ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion

Platelet/endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kD member of the Ig gene superfamily that is expressed on the surface of circulating platelets, monocytes, neutrophils, and selective T-cell subsets. It is also a major component of the endothelial cell intercellular junction. Previous studies have shown that cross-linking PECAM-1 on the surface of leukocytes results in the activation of adhesion molecules of both the β1 and β2integrin family. In addition, the process of leukocyte transendothelial migration appears to be mediated, at least in part, by homophilic adhesive interactions that take place between leukocyte and endothelial cell junctional PECAM-1 molecules. However, little is known about the functional role of this membrane glycoprotein in human platelets. In the present study, we examined the effects of PECAM-1 engagement on integrin-mediated platelet-extracellular matrix or platelet-platelet interactions. Bivalent, but not monovalent, anti–PECAM-1 monoclonal antibodies (MoAbs) specific for membrane-proximal Ig-homology domain 6 significantly augmented platelet deposition (increased surface coverage) and aggregation (increased average size) onto extracellular matrix, under both oscillatory or defined low shear flow conditions (200 s−1) in a modified cone and plate viscometer. Moreover, bivalent anti-domain 6 MoAbs were capable of serving as costimulatory agonists to markedly enhance both adenosine diphosphate (ADP)- and platelet activating factor (PAF)-induced platelet aggregation responses. These antibodies appeared to act via outside-in signal transduction through PECAM-1, as evidenced by the fact that their binding (1) led to conformational changes in the αIIbβ3 integrin complex, (2) induced surface expression of P-selectin, and (3) resulted in the tyrosine phosphorylation of PECAM-1. Together, these data support a role for PECAM-1 in cellular activation and suggest that PECAM-1 may serve as a costimulatory agonist receptor capable of modulating integrin function in human platelets during adhesion and aggregation.

scholarly journals The Synaptic Cell Adhesion Molecule, SynCAM1, Mediates Astrocyte-to-Astrocyte and Astrocyte-to-GnRH Neuron Adhesiveness in the Mouse Hypothalamus

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2353-2363 ◽  
Author(s):  
Ursula S. Sandau ◽  
Alison E. Mungenast ◽  
Jack McCarthy ◽  
Thomas Biederer ◽  
Gabriel Corfas ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Genetic Network ◽  
Dominant Negative ◽  
Gnrh Neuron ◽  
Transgenic Expression ◽  
Erbb4 Receptor ◽  
Gnrh Neurons ◽  
Membrane Spanning

We previously identified synaptic cell adhesion molecule 1 (SynCAM1) as a component of a genetic network involved in the hypothalamic control of female puberty. Although it is well established that SynCAM1 is a synaptic adhesion molecule, its contribution to hypothalamic function is unknown. Here we show that, in addition to the expected neuronal localization illustrated by its presence in GnRH neurons, SynCAM1 is expressed in hypothalamic astrocytes. Cell adhesion assays indicated that SynCAM is recognized by both GnRH neurons and astrocytes as an adhesive partner and promotes cell-cell adhesiveness via homophilic, extracellular domain-mediated interactions. Alternative splicing of the SynCAM1 primary mRNA transcript yields four mRNAs encoding membrane-spanning SynCAM1 isoforms. Variants 1 and 4 are predicted to be both N and O glycosylated. Hypothalamic astrocytes and GnRH-producing GT1-7 cells express mainly isoform 4 mRNA, and sequential N- and O-deglycosylation of proteins extracted from these cells yields progressively smaller SynCAM1 species, indicating that isoform 4 is the predominant SynCAM1 variant expressed in astrocytes and GT1-7 cells. Neither cell type expresses the products of two other SynCAM genes (SynCAM2 and SynCAM3), suggesting that SynCAM-mediated astrocyte-astrocyte and astrocyte-GnRH neuron adhesiveness is mostly mediated by SynCAM1 homophilic interactions. When erbB4 receptor function is disrupted in astrocytes, via transgenic expression of a dominant-negative erbB4 receptor form, SynCAM1-mediated adhesiveness is severely compromised. Conversely, SynCAM1 adhesive behavior is rapidly, but transiently, enhanced in astrocytes by ligand-dependent activation of erbB4 receptors, suggesting that erbB4-mediated events affecting SynCAM1 function contribute to regulate astrocyte adhesive communication.

Sign in / Sign up

Export Citation Format

Share Document