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Séminaire - Monica Sousa & Casper Hoogenraad ; 2 conférences à 10h30 et 11h30The neuronal and actin commitment: why do neurons need rings? / Cytoskeleton-based mechanisms underlying the biology and diseases of the nervous system

Abstract :

 Monica Sousa:
The discovery of actin rings in the subcortical cytoskeleton of the axon shaft and dendrites has expanded our understanding on actin organization in neurons. However, the mechanisms regulating actin ring nucleation, assembly and function remain largely elusive. Elucidating the role of actin-binding proteins in the biology of neuronal actin rings has a large potential to uncover new mechanisms of neuronal physiology that may increase our knowledge on axon degeneration and regeneration. In this seminar the role of the actin-capping protein adducin in actin rings will be presented. Our data supporting a dynamic behavior of the periodic lattice and a model in which adducin is not essential for ring assembly, but it is necessary to regulate actin filament growth within rings, and the diameter of rings and axons will be discussed. 

 Casper Hoogenraad: The formation of complex nervous systems requires cytoskeleton-based processes that coordinate proliferation, migration, and differentiation of neurons. Neuronal cells undergo major developmental changes as they migrate, develop axons and dendrites, and establish synaptic connections. The structural organization and dynamic remodeling of the neuronal cytoskeleton contribute to all these morphological and functional changes in neurons. Along with the actin cytoskeleton, the assembly, organization, and remodeling of the microtubule cytoskeleton are essential to successfully complete all the different stages of neuronal development.
Microtubule-based motor proteins such as kinesin and dynein recognize the intrinsic asymmetry of the microtubule lattice and drive transport to either the microtubule plus-end or minus-end. In various model systems it has been shown that the microtubule arrays within axon and dendrites are highly organized with respect to their intrinsic polarity and that this specific microtubule organization is essential to direct polarized cargo transport. In addition, alterations in microtubule organization and cargo trafficking have been described in many neurodegenerative diseases.

Thus, while the importance of the microtubule cytoskeleton for proper intracellular trafficking and cargo sorting is unambiguous, how the microtubule in axon and dendrites are organized in developing and mature neurons is largely unknown. I will discuss our efforts to identify the molecular processes that control microtubule organization and dynamics during the different stages of neuronal development. Our recent work indicates that the formation of parallel microtubule bundles in the proximal axon initiates neuronal polarity.

Selected publications

Publications Monica Sousa

Leite SC and Sousa MM (2016). The neuronal and actin commitment: why do neurons need rings? Cytoskeleton. In Press.
Liz MA, Mar FM, Santos TE, Pimentel HI, Marques AM, Morgado MM, Vieira S, Sousa V, Pemble H, Wittmann T, Sutherland C, Woodgett JR and Sousa MM (2014). Neuronal deletion of GSK3 increases microtubule dynamics in the growth cone and enhances axon regeneration through modulation of ----CRMP-2 activity and independently of MAP1B and CLASP2. BMC Biology 12:47.
Mar FM, Simões AR, Leite S, Morgado MM, Santos TE, Rodrigo IS, Teixeira CA, Misgeld T and -Sousa MM (2014). CNS axons globally increase axonal transport after peripheral conditioning. Journal of Neuroscience 34:5965-70.
Ferreira da Silva T, Eira J, Lopes AT, Malheiro AR, Sousa VF, Luoma A, Avila RL, J.A. Wanders JAR, Just WW, Kirschner DA, Sousa MM and Brites P (2014). Impaired Schwann cell differentiation and myelination in plasmalogen-deficient mice. Journal of Clinical Investigation 124:2560-70.

Publications Casper Hoogenraad

Kuijpers M, van de Willige D, Freal A, Chazeau A, Franker MA, Hofenk J, Cordeiro Rodrigues RJ, Kapitein LC, Akhmanova A, Jaarsma D, Hoogenraad CC (2016) Dynein regulator NDEL1 controls polarized cargo transport at the axon initial segment. Neuron, 88, 330-344

van Beuningen SF, Will L, Harterink M, Chazeau A, van Battum EY, Frias CP, Franker MA, Katrukha EA, Stucchi R, Vocking K, Antunes AT, Slenders L, Doulkeridou S, Sillevis Smitt P, Altelaar AF, Post JA, Akhmanova A, Pasterkamp RJ, Kapitein LC, de Graaff E, Hoogenraad CC (2015) TRIM46 Controls Neuronal Polarity and Axon Specification by Driving the Formation of Parallel Microtubule Arrays. Neuron 88(6):1208-26

Yau KW, van Beuningen SFB, Cunha-Ferreira I, Cloin BMC, van Battum EY, Will L, Schätzle P, Tas RP, van Krugten J, Katrukha EA, Jiang K, Wulf PS, Mikhaylova M, Harterink M, Pasterkamp RJ, Akhmanova A, Kapitein LC, Hoogenraad CC (2014) Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development. Neuron 82(5):1058-73