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Results for “Extracellular Matrix”

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PubMed1999

Inherited disorders of the extracellular matrix.

Primary and secondary defects in extracellular matrix proteins emphasize the role of these proteins in neuromuscular disorders; mutations have been found in the genes for the laminin-alpha 2 chain, for all three alpha chains of collagen VI and for integrin alpha 2. Secondary alterations in protein expression occur in association with these primary defects, and in other disorders they implicate the extracellular matrix. Animal models are helping to elucidate the function of some of these proteins, to develop therapeutic strategies and to suggest candidate proteins for other neuromuscular disorders.

Animals↗

PubMed1995

Extracellular matrix on intraocular lenses.

We examined the distribution of extracellular matrix components in the proteinaceous matrix on explanted IOLs using immunohistochemistry to clarify the nature of proteinaceous deposits on the surfaces of IOLs. We examined 15 polymethylmethacrylate (PMMA) IOLs and one silicone IOL explanted from patients. The IOLs were immunostained for cellular fibronectin, types I and IV collagen, and vitronectin. Various amounts of fibronectin, types I and IV collagen, and vitronectin were detected in the extracellular matrix on all IOLs with cellular deposits. Types I and IV collagen and cellular fibronectin were present in the extracellular matrix and were probably the products of cells adhering to the IOLs. Vitronectin in the fibrous extracellular matrix appeared to represent an adsorption material derived from the aqueous humor. These proteinaceous deposits associated with cellular deposits indicate unsuccessful formation of granulation tissue and could influence IOL biocompatibility.

Adult↗

PubMed1996

Characterizations of the extracellular matrix and proteinase inhibitor content of human myoepithelial tumors.

Myoepithelial tumors are intriguing low-grade neoplasms that exhibit the property of accumulating an abundant extracellular matrix. Because accumulation of an extracellular matrix represents an important exception to the rule of matrix degradation otherwise exhibited by the vast majority of human epithelial neoplasms, this study investigated the composition of this matrix to gain insight into the biological behavior of this class of neoplasms. Several different human myoepithelial tumors and their derived cell lines and xenografts were thus examined by ultrastructural, immunohistochemical, molecular, and biochemical methods. Results indicated that although the extracellular matrix of these tumors contains some basement membrane components such as laminin, nidogen, and heparan sulfate proteoglycan (8%), it is also largely cartilagenous in nature, containing large amounts of chondroitin sulfate proteoglycan (78%). In addition to extracellular matrix structural proteins, myoepithelial cells secreted relatively large amounts of proteinase inhibitors including maspin, protease nexin II, alpha1-antitrypsin, a 31-kd serine proteinase inhibitor, and TIMP-1. Immunolocalization and extraction studies further demonstrated that protease nexin II and alpha1-antitrypsin especially accumulated within the myoepithelial extracellular matrix. In addition, protease nexin II likely underwent extracellular in vivo processing to a 95-kd product retaining full proteinase inhibitor activity. These specific biochemical observations unite the classes of myoepithelial tumors, confer an anti-invasive property to their extracellular matrix, and likely contribute to their low-grade biological behavior.

Adenocarcinoma↗

PubMed1994

Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part IV: Effects on expression of extracellular matrix genes.

Increased deposition of lung extracellular matrix in terminal airways is associated with chronic ozone exposure. In situ hybridization was used to assess whether long-term ozone exposure causes elevated and continued expression of genes coding for connective tissue proteins. Accessory lobes were removed from the animals exposed to 0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone for 20 months as part of the National Toxicology Program (NTP)/HEI Collaborative Ozone Project. The lungs were perfused fixed under physiologic pressure and processed for in situ hybridization. Sections were hybridized with 35S-labeled probes for messenger RNA (mRNA) coding for various matrix proteins, including collagen types I and III, elastin, and fibronectin, and for interstitial collagenase, a matrix metalloproteinase. Fetal rat lung was used as a positive control for hybridization. No signal for any mRNA was detected in terminal airway stromal cells of lungs from animals exposed to ozone for 20 months or control animals breathing clean air. In all samples from animals exposed to ozone for 20 months and control animals, only a very weak signal was seen in occasional cells within the interstitial spaces around large airways and blood vessels. In contrast, a strong signal for matrix-related mRNA was detected in fetal lung tissue. These findings indicate that active or enhanced matrix production is turned off in the adult animals used in the ozone studies, suggesting that the increase in matrix deposition results from a transient and early fibrotic response. Indeed, signal for type I procollagen and tropoelastin mRNAs was seen in alveolar septal cells in lungs of rats exposed to ozone for two months. No signal was seen in alveolar cells of age-matched control animals. (These animals, exposed for two months, and age-matched controls were from earlier studies supported by the HEI.) These findings indicate that ozone mediates a transient fibrotic response that results in a sustained increase in lung extracellular matrix. Confirmation of this hypothesis would require additional studies using animals exposed to ozone for shorter times.

Administration, Inhalation↗

PubMed2001

Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor-binding protein-related protein 2) in human fibroblasts: a potential mechanism for expansion of extracellular matrix in diabetes mellitus.

Expansion of extracellular matrix with fibrosis occurs in many tissues as part of the end-organ complications in diabetes, and advanced glycosylation end products (AGE) are implicated as one causative factor in diabetic tissue fibrosis. Connective tissue growth factor (CTGF), also known as insulin-like growth factor-binding protein-related protein-2 (IGFBP-rP2), is a potent inducer of extracellular matrix synthesis and angiogenesis and is increased in tissues from rodent models of diabetes. The aim of this study was to determine whether CTGF is up-regulated by AGE in vitro and to explore the cellular mechanisms involved. AGE treatment of primary cultures of nonfetal human dermal fibroblasts in confluent monolayer increased CTGF steady state messenger RNA (mRNA) levels in a time- and dose-dependent manner. In contrast, mRNAs for other IGFBP superfamily members, IGFBP-rP1 (mac 25) and IGFBP-3, were not up-regulated by AGE. The effect of the AGE BSA reagent on CTGF mRNA was due to nonenzymatic glycosylation of BSA and, using neutralizing antisera to AGE and to the receptor for AGE, termed RAGE, was seen to be due to late products of nonenzymatic glycosylation and was partly mediated by RAGE. Reactive oxygen species as well as endogenous transforming growth factor-beta1 could not explain the AGE effect on CTGF mRNA. AGE also increased CTGF protein in the conditioned medium and cell-associated CTGF. Thus, AGE up-regulates the profibrotic and proangiogenic protein CTGF (IGFBP-rP2), a finding that may have significance in the development of diabetic complications.

Cells, Cultured↗

PubMed2002

Matrilin-2 interacts with itself and with other extracellular matrix proteins.

Matrilin-2 is a component of extracellular filamentous networks. To study the interactions by which it can be integrated into such assemblies, full-length and truncated forms of matrilin-2 were recombinantly expressed in HEK-293 cells and purified from conditioned medium. The recombinant proteins, when used in interaction assays, showed affinity to matrilin-2 itself, but also to other collagenous and non-collagenous extracellular matrix proteins. The interaction between matrilin-2 and collagen I was studied in greater detail and could be shown to occur at distinct sites on the collagen I molecule and to have a K (D) of about 3 x 10(-8) M. Interactions with some non-collagenous protein ligands were even stronger, with matrilin-2 binding to fibrillin-2, fibronectin and laminin-1-nidogen-1 complexes, with K (D) values in the range of 10(-8)-10(-11) M. Co-localization of matrilin-2 with these ligands in the dermal-epidermal basement membrane, in the microfibrils extending from the basement membrane into the dermis, and in the dermal extracellular matrix, indicates a physiological relevance of the interactions in the assembly of supramolecular extracellular matrix structures.

Base Sequence↗

PubMed1984

The role of intermolecular disulfide bonding in deposition of GP140 in the extracellular matrix.

Human WI-38 fibroblasts in cultures synthesized at least three molecular forms of the major, extracellular matrix glycoprotein (GP), GP140: (a) cytoplasmic GP140 (1.2 ng of GP140/micrograms of cell protein) was detergent-soluble, underglycosylated, and possessed detectable levels of intermolecular disulfide bonding; (b) matrix GP140 (3.6 ng of GP140/micrograms of cell protein) was detergent-insoluble, more highly glycosylated and polymerized by intermolecular disulfide bonding, and co-distributed in the extracellular matrix with fibronectin; and (c) released GP140 (2 ng of GP140/micrograms of cell protein per 24 h) was recovered in the conditioned culture media and lacked intermolecular disulfide bonding. Cytoplasmic GP140 was the immediate biosynthetic precursor of the matrix form of GP140. In addition, various human adult and fetal tissues contained a form of GP140 that resembled the fibroblast matrix GP140 in the degree of intermolecular disulfide bonding, relative molecular mass, and immunological reactivity. Analysis of the sequence of events in assembly of GP140 and fibronectin in the extracellular matrix detected the following: (a) fibronectin was first to appear in the extracellular matrix; (b) GP140 accumulated in the cytoplasm, then deposited in the extracellular matrix and co-aligned with the established fibronectin; and (c) maturation of the extracellular matrix proceeded by continued intermolecular disulfide bonding. To evaluate possible roles for intermolecular disulfide bonding in cell interactions, a unique assay system was utilized based on the ability of labeled cells to incorporate radioactive matrix components into a biotinylated exogenous matrix. Precipitation of the biotinylated matrix from extracts of the cultures using avidin indicated: (a) disulfide bonding of radioactive GP140 and fibronectin into the exogenous biotinylated matrix required cell contact with the matrix. The newly deposited GP140 and fibronectin derived from the cells and not from GP140 and fibronectin present in the conditioned culture media. (b) Pro-alpha 1 and Pro-alpha 2 procollagens, present in the culture media, bound to the exogenous matrix in a noncovalent manner and were independent of cell contact. (c) SV40 transformed cells (WI-38 VA13) synthesized released form GP140 but did not deposit GP140 into the biotinylated matrix.

Cell Line↗

PubMed1995

The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.

Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho family of GTPases.

3T3 Cells↗

PubMed1993

[Pathophysiology of cytoskeleton and extracellular matrix in failing myocardium].

Cytoskeleton of myocytes and extracellular matrix play an essential role for maintaining cellular function. Alterations in humoral factors observed in heart failure, e.g., excess of plasma norepinephrine and angiotensin II, injure the microtubule structure probably through Ca overload and increase the collagen synthesis of the cardiac fibroblast. Recent studies demonstrated that network structures of microtubules and intermediate filaments are disrupted in the myocardium obtained from patients with heart failure. Changes in cytoskeletons and extracellular matrix may affect the contractile function, since they organize the intra- and inter-cellular architectures. Pathophysiological roles of cytoskeletons and extracellular matrix in failing hearts deserve further studies.

Angiotensin II↗

PubMed1999

Regulation of extracellular matrix gene expression by mechanical stress.

Extracellular matrix (ECM) is the substrate for cell adhesion, growth, and differentiation, and it provides mechanical support to tissues. It is well known that connective tissue cells adapt their ECM to changes in mechanical load, as seen, e.g. during bone remodeling or wound healing. A feedback mechanism must exist by which cells that sense mechanical stress via their substrate respond by an altered pattern of protein expression, and thus remodel the ECM to meet changing mechanical requirements. What signals are triggered in connective tissue cells by mechanical stress, and how do such stimuli affect the expression of specific ECM proteins? The evidence will be reviewed that integrins, the transmembrane adhesion and signaling receptors which physically link ECM to the cytoskeleton, might be key players in transducing mechanical signals, presumably via MAP kinase and NF-kappaB pathways. At the far end of the response, there is evidence for regulation at the level of gene transcription. For example, the production of tenascin-C and collagen XII, two ECM proteins typical of tendons and ligaments, is high in fibroblasts attached to a stretched collagen matrix, but suppressed in cells on a relaxed matrix. The response to a change in stretch is rapid and reversible, and is reflected on the mRNA level. Both the tenascin-C and the collagen XII gene promoters contain 'stretch-responsive' enhancer regions with similarity to 'shear stress response elements' in other genes. The precise signal pathways converging on these mechano-responsive enhancer elements remain to be elucidated.

Adaptation, Physiological↗

PubMed1998

VLA-5 is expressed by mouse and human long-term repopulating hematopoietic cells and mediates adhesion to extracellular matrix protein fibronectin.

Fibronectin (FN), an extracellular matrix protein, is involved in the adhesion and migration of hematopoietic cells and has been shown to enhance retroviral gene transfer into primitive hematopoietic cells by co-localization of target cells and retrovirus when used as a substrate in vitro. We have previously found that mouse hematopoietic stem cells could be transduced on a FN fragment that included the recognition sequence Arg-Gly-Asp (RGD), suggesting that stem cells may express the integrin very late antigen (VLA)-5. To address this, we investigated the binding of mouse and human hematopoietic cells to recombinant peptides that contained one or a combination of the three principle cell-binding domains of FN. These domains included the VLA-5- binding sequence RGD, the VLA-4-binding site CS1, and the high affinity heparin-binding domain. Here we show that mouse long-term in vivo repopulating stem cells, as well as primitive human NOD/SCID mouse repopulating cells, can bind extracellular matrix protein FN by using integrin VLA-5 in vitro. This binding is specific and can be inhibited by antibodies to VLA-5. In addition, preincubation of BM cells with peptide CH-296, which contains all three primary FN-binding domains, decreased the engraftment of cells in the bone marrow in vivo, while intravenous injection of the same peptide induced an increase of progenitor cells in the spleen. In summary, our data demonstrate that VLA-5 is expressed on primitive mouse and human hematopoietic cells and suggest that there may be significant cooperation between integrin receptors and proteoglycan molecules in the engraftment of bone marrow cells and hematopoietic cell adhesion in vivo.

Animals↗

PubMed2004

[Control of calcification by extracellular matrix].

Physiological calcification begins from crystallization of hydroxyapatite in extracellular matrix of both bones and teeth. Because calcification is exactly the extracellular event, organic components of extracellular matrix play important roles in control of calcification. The authors discuss the molecular regulation of calcification by organic components of extracellular matrix, focusing on the mineral/organic interaction.

1-Carboxyglutamic Acid↗

PubMed1997

Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules.

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed on cancer cell membranes and activates the zymogen of MMP-2 (gelatinase A). We have recently isolated MT1-MMP complexed with tissue inhibitor of metalloproteinases 2 (TIMP-2) and demonstrated that MT1-MMP exhibits gelatinolytic activity by gelatin zymography (Imai, K., Ohuchi, E., Aoki, T., Nomura, H., Fujii, Y., Sato, H., Seiki, M., and Okada, Y. (1996) Cancer Res. 56, 2707-2710). In the present study, we have further purified to homogeneity a deletion mutant of MT1-MMP lacking the transmembrane domain (DeltaMT1) and native MT1-MMP secreted from a human breast carcinoma cell line (MDA-MB-231 cells) and examined their substrate specificities. Both proteinases are active, without any treatment for activation, and digest type I (guinea pig), II (bovine), and III (human) collagens into characteristic 3/4 and 1/4 fragments. The cleavage sites of type I collagen are the Gly775-Ile776 bond for alpha1(I) chains and the Gly775-Leu776 and Gly781-Ile782 bonds for alpha2(I) chains. DeltaMT1 hydrolyzes type I collagen 6.5- or 4-fold more preferentially than type II or III collagen, whereas MMP-1 (tissue collagenase) digests type III collagen more efficiently than the other two collagens. Quantitative analyses of the activity of DeltaMT1 and MMP-1 indicate that DeltaMT1 is 5-7.1-fold less efficient at cleaving type I collagen. On the other hand, gelatinolytic activity of DeltaMT1 is 8-fold higher than that of MMP-1. DeltaMT1 also digests cartilage proteoglycan, fibronectin, vitronectin and laminin-1 as well as alpha1-proteinase inhibitor and alpha2-macroglobulin. The activity of DeltaMT1 on type I collagen is synergistically increased with co-incubation with MMP-2. These results indicate that MT1-MMP is an extracellular matrix-degrading enzyme sharing the substrate specificity with interstitial collagenases, and suggest that MT1-MMP plays a dual role in pathophysiological digestion of extracellular matrix through direct cleavage of the substrates and activation of proMMP-2.

Collagen↗

PubMed1992

Lymphocyte migration through extracellular matrix.

The movement of lymphocytes through extracellular matrix (ECM) is an essential component of normal traffic and infiltration into inflammatory sites. This review surveys current knowledge of the mechanisms of lymphocyte migration through ECM, most of which was derived from work with in vitro models of basement membranes, interstitial stroma, or their constituent components. Normal lymphocyte motility is an extremely plastic property. Naive lymphocytes tend to be unresponsive to ECM components and many chemoattractants, but when exposed to antigens, artificial mitogens and certain lymphokines, they rapidly acquire locomotory capacity, which is expressed as increased polarity, adhesiveness, invasiveness and chemotactic response. Acquisition of locomotory capacity is associated with the G0/G1 transition, and activation of protein kinase C appears to be a key event. Preliminary evidence indicates that mitogenesis and differentiation to the memory phenotype trigger a long-lasting, possibly permanent elevation of locomotory response to ECM. Receptors for fibronectin, laminin and collagens I and IV have been implicated as mediators of lymphocyte motility, but these receptors have not been characterized in detail. Heparanases facilitate T cell movement through the basement membrane, but the role of proteases has not yet been defined. Major gaps remain in our understanding of the connection between in vitro models and specific stages of the infiltration process in vivo and of motility regulation at the molecular level.

Animals↗

PubMed2001

The extracellular matrix in multiple sclerosis: an update.

Extracellular matrix (ECM) molecules play important roles in the pathobiology of the major human central nervous system (CNS) inflammatory/demyelinating disease multiple sclerosis (MS). This mini-review highlights some recent work on CNS endothelial cell interactions with vascular basement membrane ECM as part of the cellular immune response, and roles for white matter ECM molecules in demyelination and remyelination in MS lesions. Recent basic and clinical investigations of MS emphasize axonal injury, not only in chronic MS plaques, but also in acute lesions; progressive axonal degeneration in normal-appearing white matter also may contribute to brain and spinal cord atrophy in MS patients. Remodeling of the interstitial white matter ECM molecules that affect axon regeneration, however, is incompletely characterized. Our ongoing immunohistochemical studies demonstrate enhanced ECM versican, a neurite and axon growth-inhibiting white matter ECM proteoglycan, and dermatan sulfate proteoglycans at the edges of inflammatory MS lesions. This suggests that enhanced proteoglycan deposition in the ECM and axonal growth inhibition may occur early and are involved in expansion of active lesions. Decreased ECM proteoglycans and their phagocytosis by macrophages along with myelin in plaque centers imply that there is "injury" to the ECM itself. These results indicate that white matter ECM proteoglycan alterations are integral to MS pathology at all disease stages and that they contribute to a CNS ECM that is inhospitable to axon regrowth/regeneration.

Axons↗

PubMed2004

Red wine administration to apolipoprotein E-deficient mice reduces their macrophage-derived extracellular matrix atherogenic properties.

Proteoglycans (PGs) from the arterial extracellular matrix (ECM) contribute to the trapping of LDL and oxidized LDL (Ox-LDL) in the arterial wall, a phenomenon called "lipoprotein retention". Moreover, we have shown that subsequent to their binding to the matrix, LDL and Ox-LDL are taken up by macrophages. Oxidative stress significantly increases macrophage secretion of ECM-PGs, lipoprotein binding to the ECM and the uptake of ECM-retained lipoproteins by macrophages. The aim of the present study was to determine whether red wine administration to atherosclerotic mice would affect their peritoneal macrophage-derived extracellular matrix properties, such as the glycosaminoglycan content and the ability to bind LDL. In addition, we questioned the ability of LDL bound to the mice peritoneal macrophages-derived ECM to be taken up by macrophages. Red wine administration to atherosclerotic mice did not affect the mice peritoneal macrophages-derived ECM glycosaminoglycan content but it significantly reduced the mice peritoneal macrophages-derived ECM ability to bind LDL and the subsequent uptake of ECM-retained LDL by the macrophages. The present study thus clearly demonstrated the inhibitory effect of red wine consumption by E0 mice on their peritoneal macrophage-derived extracellular matrix atherogenic properties.

Animals↗

PubMed2003

Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): co-expression in metastatic serous ovarian carcinoma.

Activation or suppression of intracellular signaling via the mitogen-activated protein kinase (MAPK) family has been linked to expression of matrix metalloproteinases (MMP) in experimental models, but this association has not been demonstrated in clinical material. The objective of this study was to investigate the possible association between expression and activity of MMP, expression of the MMP inducer EMMPRIN, and the expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) and high osmolarity glycerol response kinase (p38) in effusions from patients diagnosed with serous ovarian carcinoma. MAPK level and activity were studied in 55 effusions using immunoblotting. MMP-1, MMP-2, MMP-9 and EMMPRIN expression was studied using immunocytochemistry (ICC) and mRNA in situ hybridization (ISH). The gelatinolytic activity of MMP-2 and MMP-9 was measured by zymography. ERK and phospho-ERK (p-ERK) were detected in 54/55 (98%) and 50/55 (91%) specimens, respectively. JNK and p-JNK were detected in 53/55 (96%) and 38/55 (69%) specimens, respectively. p38 was expressed in 54/55 (98%) specimens, and its phosphorylated form was found in 51/55 (92%). MMP-2 mRNA expression (P = 0.048), protein expression (P = 0.046) and gelatinolytic activity (P = 0.039) correlated with ERK phosphorylative activity. MMP-2 activity also correlated with p38 activity (P = 0.017). MMP-9 protein expression correlated with phosphorylation of p38 (P = 0.046), but enzyme activity showed inverse relationship with both p-ERK (P = 0.05) and p-p38 (P = 0.033) expression. EMMPRIN expression correlated with MMP-1 (P < 0.001), MMP-2 (P = 0.042) and MMP-9 (P = 0.029) expression, as well as with ERK activity (P = 0.001). Our results present the first evidence of a possible link between MAPK signaling and MMP expression and activity in vivo. These data may expand our understanding regarding the mechanisms by which MMP synthesis is regulated in effusions and possibly affect treatment strategies for this form of malignancy.

Adult↗

PubMed1987

Adhesion plaques: sites of transmembrane interaction between the extracellular matrix and the actin cytoskeleton.

In this paper we review what is known about the organization of adhesion plaques, the regions where cells in culture adhere most tightly to the underlying substratum. These specialized areas of the plasma membrane serve as attachment sites for stress fibres. A major objective has been to determine how microfilament bundles are anchored at such regions. In their morphology and composition adhesion plaques resemble the adhesions fibroblasts make to the extracellular matrix. Some extracellular matrix components have been identified on the outside face of adhesion plaques. Within the plasma membrane of adhesion plaques, extracellular matrix receptors, such as the fibronectin receptor (integrin), have been identified. This transmembrane glycoprotein complex has been shown to bind the cytoplasmic protein talin, which, in turn, associates with vinculin. These proteins establish a transmembrane chain of attachment between the extracellular matrix and the cytoskeleton, although how the actin filaments interact with these components remains to be determined. Besides having a structural function, adhesion plaques may also be regions where regulatory signals are transmitted across the membrane. Consistent with this idea has been the finding that various tyrosine kinases and a calcium-dependent protease are concentrated at the cytoplasmic aspect of adhesion plaques. Furthermore, several adhesion plaque proteins become phosphorylated during cell transformation by Rous sarcoma virus. In future work it will be important to determine how such modifications affect the interactions of these proteins and the stability of adhesion plaques.

Actins↗