MAP6 protects, regulates and curls microtubules
Mardi 10 novembre 2015 13:00
- Duree : 1 heure
Lieu : Amphithéâtre Serge Kampf, Grenoble Institut des Neurosciences (GIN) - Bât. Edmond J. Safra, Chemin Fortune Ferrini CHU, La Tronche
Orateur : Christian DELPHIN (équipe Andrieux)
Microtubules are dynamic structures that present the peculiar characteristic to be ice-cold-labile in vitro. In vivo,
microtubules are protected from ice-cold induced depolymerization by the widely expressed MAP6/STOP family
of proteins. However, the mechanism by which MAP6 stabilizes microtubules at 4°C has not been identified. We
show here that in cells, MAP6-F binding to- and stabilization of microtubules is temperature-dependent and very
dynamic, suggesting a direct effect of the temperature on the formation of microtubule/MAP6 complex. We also
demonstrate, using purified proteins that MAP6-F binds directly to microtubules through its Mc domain. This
binding is temperature-dependent and coincides with progressive conformational changes of the Mc domain as
revealed by circular dichroism. Thus, MAP6 might serve as a temperature sensor adapting its conformation
according to the temperature to maintain the cellular microtubule network integrity in organisms exposed to
temperature decrease.
In addition to the Mc domain, the neuronal MAP6 isoforms MAP6E and MAP6N possess microtubules binding
modules (Mn) that stabilize microtubules at 37°C in vivo. Using purified recombinant proteins, we showed that
MAP6N interacts with tubulin dimers and microtubules and started an in vitro analysis of MAP6N effects on
microtubule dynamics. At low concentration (100 nM), MAP6N favors microtubule plus-end growth by
stimulating the growth speed and the rescue frequency while inhibiting catastrophe events. More surprisingly,
MAP6N also has an effect on microtubule minus-end dynamics. Indeed, it inhibits both minus-end growth and
shrinking. At higher concentration, MAP6N stimulates microtubule nucleation and unexpectedly induces
microtubule curling. Preliminary data indicate that MAP6N effects on microtubule dynamics involve essentially
the Mn modules. On the contrary, microtubule nucleation and curling are more integrated MAP6N functions.
Contact : yves.goldberg@ujf-grenoble.fr
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