INVESTIGADORES
WEISSMANN Carina
congresos y reuniones científicas
Título:
Analysis of photoactivatable tau proteins in living cells
Autor/es:
CARINA WEISSMANN; ANNA HILLJE; HANS-JÜRGEN REYHER; HEINZ-JÜRGEN STEINHOFF; ROLAND BRANDT
Lugar:
Witten, Alemania
Reunión:
Conferencia; International Conference of the Gesellschaft für Biochemie und Molekularbiologie 2006; 2006
Institución organizadora:
Study Group Neurochemistry
Resumen:
Tau is a cytoskeletal protein that is mainly enriched in
axons where it is thought to regulate microtubule dynamics.
Tau is also involved in many diseases referred to as
"tauopathies" which includes Alzheimer´s disease (AD).
In AD, tau is redistributed to the somato-dendritic compartment
and becomes aggregated.
To study the effect of tau proteins (a wild type tau and a
R406W mutation present in cases of Frontotemporal
dementia and parkinsonism linked to chromosome 17,
FTDP-17) in living cells, different PC12 cell lines expressing
the proteins were created. With the purpose of studying
their mobility, the proteins were fused to a
photoactivatable molecule.
The stable lines showed differences in their state of phosphorylation
as analyzed by western blots, where mutant
tau exhibited a hypophosphorylated state. The development
of neurites after NGF treatment showed differences
in the kinetics in that mutant-tau-expressing cells developed
processes earlier, which also became longer
throughout time.
Finally, photoactivation experiments revealed that the
mutant tau line shows a higher proportion of stationary
tau proteins over time suggesting a potential mechanism
for the different distribution of mutant proteins or differently
phosphorylated proteins in tauopathies. This finding
was not related to an effect on microtubule stability as
could be seen in western blots by analyzing the degree of
tubulin acetylation.
Taken together, the data demonstrate that photoactivatable
tau proteins provide a useful tool to analyze dynamic
properties (with a supportive biochemical correlate) in a
living neuronal cell model scenario to help determine the
effects of different tau mutations in neurodegenerative
diseases.