Involvement of Cell Surface HSP90 in Cell Migration Reveals a Novel Role in the Developing Nervous System
Heat shock protein HSP90 plays important roles in cellular regulation, primarily as a chaperone for a number of key intracellular proteins. We report here that the two HSP90 isoforms, α and β, also localize on the surface of cells in the nervous system and are involved in their migration. A 94-kDa...
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Veröffentlicht in: | The Journal of biological chemistry 2004-10, Vol.279 (44), p.45379-45388 |
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Sprache: | eng |
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Zusammenfassung: | Heat shock protein HSP90 plays important roles in cellular regulation, primarily as a chaperone for a number of key intracellular
proteins. We report here that the two HSP90 isoforms, α and β, also localize on the surface of cells in the nervous system
and are involved in their migration. A 94-kDa surface antigen, the 4C5 antigen, which was previously shown to be involved
in migration processes during development of the nervous system, is shown to be identical to HSP90α using mass spectrometry
analysis. This identity is further confirmed by immunoprecipitation experiments and by induction of 4C5 antigen expression
in heat shock-treated embryonic rat brain cultures. Moreover, immunocytochemistry on live cerebellar rat cells reveals cell
surface localization of both HSP90α and -β. Cell migration from cerebellar and sciatic nerve explants is inhibited by anti-HSP90α
and anti-HSP90β antibodies, similarly to the inhibition observed with monoclonal antibody 4C5. Moreover, immunostaining with
rhodamine-phalloidin of migrating Schwann cells cultured in the presence of antibodies against both α and β isoforms of HSP90
reveals that HSP90 activity is associated with actin cytoskeletal organization, necessary for lamellipodia formation. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M405486200 |