MAP6-F is a temperature sensor that directly binds to and protects microtubules from cold-induced depolymerization.
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. Moreover, the microtubule cold sensitivity and therefore the needs for microtubule stabilization in the wide range of temperatures between 4 and 37 °C are unknown. This is of importance as body temperatures of animals can drop during hibernation or torpor covering a large range of temperatures. Here, we show that in the absence of MAP6, microtubules in cells below 20 °C rapidly depolymerize in a temperature-dependent manner whereas they are stabilized in the presence of MAP6. We further show 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 in organisms exposed to temperature decrease.
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France. Electronic address: christian.delphin@ujf-grenoble.fr.
Christian
C
Delphin
the European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France.
Denis
D
Bouvier
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Maxime
M
Seggio
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Emilie
E
Couriol
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Yasmina
Y
Saoudi
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Eric
E
Denarier
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Christophe
C
Bosc
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Odile
O
Valiron
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Mariano
M
Bisbal
Team 13 Dynamic and Structural Regulation of Cytoskeleton, Institut National de la Santé et de la Recherche Médicale, U836-GIN, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Isabelle
I
Arnal
Team 1 Physiopathology of Cytoskeleton; Commissariat à I'Energie Atomique, Institut National de la Santé et de la Recherche Médicale, U836-GIN iRTSV-GPC, Site Santé La Tronche, BP170, 38042 Grenoble, Cedex 9, France.
Annie
A
Andrieux
D000818:Animals; D003080:Cold Temperature; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary
C491894:MAP6 protein, human; D008869:Microtubule-Associated Proteins