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Marion BENOIST"MAP1B-dependent activation of Rac is required for AMPA receptor endocytosis during long-term depression"

Abstract :


Synaptic connections in the brain are continuously fine-tuned by adding or removing neurotransmitter receptors in response to neuronal activity.
Despite the importance of this form of synaptic plasticity for learning and memory, we still know very little of the molecular and cellular mechanisms that govern the transport of neurotransmitter receptors at synapse. It is generally accepted that rearrangements in the actin cytoskeleton are critical for the structural and functional changes of synapses during plasticity. Nevertheless, recent evidence is indicating that the microtubule cytoskeleton may also participate in the mechanisms underlining synaptic plasticity. 
In this work, we have explored potential roles of microtubule associated proteins (MAPs) in synaptic function and plasticity at hippocampal synapses. In particular, we have assessed the role of MAP1B, a neuronal cytoskeletal protein that plays critical roles in neurite and synapse development. MAP1B associates with microtubules and promotes their assembly, but it interacts also with actin in highly dynamic cellular compartments. Therefore, MAP1B is an attractive candidate to participate in events that require coordination between microtubule and actin cytoskeletons. 
Using electrophysiological recordings and imaging in neuron in culture from hypomorphous mouse mutants expressing very low levels of the MAP1B protein, we showed that MAP1B is essential for spine maturation. With the same mutant mouse, but in adults, we also determined that MAP1B is involved in long term depression (LTD) induced by NMDA and metabotropic glutamate receptors in hippocampal CA1 neurons. Using a combination of biochemistry, fluorescence live imaging experiments and electrophysiological techniques, we have investigated the molecular mechanisms that link MAP1B with these specific forms of synaptic plasticity. First we saw that MAP1B’s expression is regulated upon synaptic plasticity and that it is mobilized from the microtubules over NMDAR activation. Then, looking at trafficking of GluA2 during LTD we showed that MAP1B is needed for the first step of AMPAR removal from the spine. Finally we establish that MAP1B acts during LTD via small GTPase regulation. 
We believe that these studies highlight the role of microtubule associated proteins in physiological processes of cognitive function

Selected publications

Benoist, M., Palenzuela, R., Rozas, C., Rojas, P., Morales, B., Gonzalez-Billault, C., Avila, J and Esteban, J.A. MAP1B-dependent activation of Rac is required for AMPA receptor endocytosis during long-term depression. Under revision Nat. Neurosc.
Tortosa, E., Montenegro-Venegas, C., Benoist, M., Hartel, S., Gonzalez-Billault, C., Esteban, J.A., and Avila, J. (2011). Microtubule-associated protein 1B (MAP1B) is required for dendritic spine development and synaptic maturation. J Biol Chem 286, 40638-40648.
Jurado, S., Benoist, M., Lario, A., Knafo, S., Petrok, C.N., and Esteban, J.A. (2010). PTEN is recruited to the postsynaptic terminal for NMDA receptor-dependent long-term depression. EMBO J 29, 2827-2840.
Benoist, M., Baude, A., Tasmadjian, A., Dargent, B., Kessler, J.P., and Castets, F. (2008). Distribution of zinedin in the rat brain. J Neurochem 106, 969-977.
Benoist, M., Gaillard, S., and Castets, F. (2006). The striatin family: a new signaling platform in dendritic spines. J Physiol Paris 99, 146-153.

Nathalie Sans