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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Regulation of the microtubule dynamics and structure by the Adenomatous Polyposis Coli protein studied by electron microscopy

Objectifs

Our main goal is to understand the microtubule regulation by APC alone and in complex with other microtubule binding proteins. We will determine the effect of these complexes on microtubule dynamics, structure and decoration.

Résumé

The Adenomatous Polyposis Coli protein (APC) is a scaffold protein related to a panel of cellular processes. In brain, for example, APC is abundantly expressed and is involved in the development of the axonal growth cone and architecture of the post-synaptic compartment. A defect in APC gene can be linked to neurologic disorders and intellectual disabilities. APC is also characterized as a tumor suppressor: mitotic defects are indeed associated with APC mutations leading to an incorrect cell division and future cancers. These functions are all connected to the cytoskeleton interacting properties of APC. Our interest is to understand how APC regulates the cytoskeleton dynamics and structure, directly by interacting with the microtubules or via its interaction with diverse proteins (motor complex, end-binding proteins) that can influence the dynamic instability of microtubules. We will use biochemistry and electron microscopy to dissect these interactions at the atomic level.

Méthodes

We will apply an in vitro approach combining directed mutagenesis, biochemistry, video microscopy and electron microscopy (negative staining, cryo-EM, cryo-tomography).

Références

  • Prezel E, Elie A, Delaroche J, Stoppin-Mellet V, Bosc C, Serre L, Fourest-Lieuvin A, Andrieux A, Vantard M, Arnal I. (2018) Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles. Mol Biol Cell. 29:154-165
  • Ramirez-Rios S, Serre L, Stoppin-Mellet V, Prezel E, Vinit A, Courriol E, Fourest-Lieuvin A, Delaroche J, Denarier E, Arnal I. (2017) A TIRF microscopy assay to decode how tau regulates EB's tracking at microtubule ends. Methods Cell Biol. 141:179-197
  • Elie A, Prezel E, Guérin C, Denarier E, Ramirez-Rios S, Serre L, Andrieux A, Fourest-Lieuvin A, Blanchoin L & Arnal I. (2015) Tau co-organizes dynamic microtubule and actin networks. Sci. Rep. 5 :9964

Domaines d'expertise requis

Biochemistry, structural biology

Contacts

Laurence SERRE, CNRS Researcher
Email : laurence.serre@univ-grenoble-alpes.fr

Mise à jour le 31 mai 2018

Contacts

Pour une candidature spontanée, envoyez un email à gincomm[at]univ-grenoble-alpes.fr ou utilisez le formulaire de contact.

Pour les stages de licence et de 3ème, voir les modalités de demande spécifiques sur les pages correspondantes. 

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