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, alpha and beta, 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 HSP90alpha 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 HSP90alpha and -beta. Cell migration from cerebellar and sciatic nerve explants is inhibited by anti-HSP90alpha and anti-HSP90beta 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 alpha and beta isoforms of HSP90 reveals that HSP90 activity is associated with actin cytoskeletal organization, necessary for lamellipodia formation.
AuthorsKaterina Sidera, Martina Samiotaki, Eleni Yfanti, George Panayotou, Evangelia Patsavoudi
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 44 Pg. 45379-88 (Oct 29 2004) ISSN: 0021-9258 [Print] United States
PMID15302889 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • HSP90 Heat-Shock Proteins
  • Membrane Proteins
  • Amino Acid Sequence
  • Animals
  • Brain (cytology, embryology)
  • Cell Movement
  • Cells, Cultured
  • Cerebellum (chemistry)
  • Cytoskeleton (chemistry)
  • HSP90 Heat-Shock Proteins (analysis, chemistry, physiology)
  • Hot Temperature
  • Immunohistochemistry
  • Membrane Proteins (physiology)
  • Molecular Sequence Data
  • Rats
  • Sciatic Nerve (chemistry)

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