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Aggregation of integrins and RhoA activation are required for Thy-1-induced morphological changes in astrocytes

Authordc.contributor.authorÁvalos, Ana María es_CL
Authordc.contributor.authorArthur, William T. 
Authordc.contributor.authorSchneider, Pascal es_CL
Authordc.contributor.authorQuest, Andrew F. G. es_CL
Authordc.contributor.authorBurridge, Keith es_CL
Authordc.contributor.authorLeyton Campos, Lisette es_CL
Admission datedc.date.accessioned2007-04-24T20:51:38Z
Available datedc.date.available2007-04-24T20:51:38Z
Publication datedc.date.issued2004-09-10
Cita de ítemdc.identifier.citationJOURNAL OF BIOLOGICAL CHEMISTRY 279 (37): 39139-39145 SEP 10 2004en
Identifierdc.identifier.issn0021-9258
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/127116
Abstractdc.description.abstractThy-1, a cell adhesion molecule abundantly expressed in mammalian neurons, binds to a beta(3)-containing integrin on astrocytes and thereby stimulates the assembly of focal adhesions and stress fibers. Such events lead to morphological changes in astrocytes that resemble those occurring upon injury in the brain. Extracellular matrix proteins, typical integrin ligands, bind to integrins and promote receptor clustering as well as signal transduction events that involve small G proteins and cytoskeletal changes. Here we investigated the possibility that the cell surface protein Thy-1, when interacting with a beta(3)-containing integrin on astrocytes, could trigger signaling events similar to those generated by extracellular matrix proteins. DI-TNC1 astrocytes were stimulated with Thy-1-Fc immobilized on beads, and increased RhoA activity was confirmed using an affinity precipitation assay. The effect of various inhibitors on the cellular response was also studied. The presence of Y-27632, an inhibitor of Rho kinase (p160ROCK), a key downstream effector of RhoA, significantly reduced focal adhesion and stress fiber formation induced by Thy-1. Similar effects were obtained when astrocytes were treated with C3 transferase, an inhibitor of RhoA. Alternatively, astrocytes were transfected with an expression vector encoding fusion proteins of enhanced green fluorescent protein with either the Rho-binding domain of Rhotekin, which blocks RhoA function, or the dominant-negative N19RhoA mutant. In both cases, Thy-1-induced focal adhesion formation was inhibited. Furthermore, we observed that RhoA activity after stimulation with soluble Thy-1-Fc molecule was augmented upon further cross-linking using protein A-Sepharose beads. The same was shown by crosslinking beta(3)-containing integrin with anti-beta(3) antibodies. Together, these results indicate that Thy-1-mediated astrocyte stimulation depended on beta(3) integrin clustering and the resulting increase in RhoA activity.en
Lenguagedc.language.isoenen
Publisherdc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCen
Keywordsdc.subjectACTIN STRESS FIBERSen
Títulodc.titleAggregation of integrins and RhoA activation are required for Thy-1-induced morphological changes in astrocytesen
Document typedc.typeArtículo de revistaen


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