IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Roles of FKBP52 and Hsp90 in Neurodifferentiation and Transdifferentiation of Astrocytes into Neurons
Autor/es:
QUINTÁ HR; GALIGNIANA MD
Lugar:
Les Diablerets
Reunión:
Conferencia; 6th International Conference on the Hsp90 Chaperone Machine (19-23 Sept 2012), Les Diablerets, Suiza; 2012
Resumen:
We have recently shown that, in undifferentiated neuronal cells, the FKBP52*Hsp90*p23 heterocomplex concentrates in a perinuclear rim associated to lamin B, where it seems to represses transcription, as judged by the poor signal generated by early mRNAs labeled with Br-UTP. When cells are stimulated with tacrolimus, rapid morphologic and biochemical changes take place including the induction of most chaperones and cochaperones (except FKBP51). After a few hours, cells become neurons. Interestingly, the FKBP52*Hsp90*p23 heterocomplex disassembles rapidly and the perinuclear area becomes transcriptionally active. Importantly, the FKBP52- and p23-free nuclear Hsp90 (originally concentrated in a large speckle) migrates to the cytoplasm and concentrates around the centrosome interacting physically with ?-tubulin. This Hsp90-based structure grows to reach 50% of the nucleus volume, and disappears three days after. In contrast to nuclear Hsp90, cytoplasmic Hsp90 is hyperacetylated, associates to HDAC6, and acts as a marker for the growing cone of the neuron. Fibers associated to p23 are born here and penetrate into the growing axon. FKBP52 plays a major role in the process since its overexpression yields longer axons and even spontaneous differentiation in the absence of the drug. On the other hand, FKBP51 shows antagonistic action. We also observed that astrocytes, usual contaminants of primary embryonic neurons, transdifferentiate into neurons with tacrolimus, a process also favored by FKBP52 and counteracted by FKBP51. It is concluded that the FKBP52*Hsp90*p23 complex is critical for the mechanism of neuronal differentiation and also for the unexpected mechanism of astrocyte transdifferentiation into neurons.