INVESTIGADORES
GALIGNIANA Mario Daniel
congresos y reuniones científicas
Título:
Roles of Hsp90 and FKBP52 in Neurodifferentiation and Transdifferentiation of Astrocytes into Neurons
Autor/es:
QUINTA HR, PIWIEN PILIPUK G, GALIGNIANA MD
Lugar:
Les Diablerets
Reunión:
Conferencia; The 6th International Conference on the Hsp90 Chaperone Machine; 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 g-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.