Jose Esteban Ph.D.
| 1301D MSRB III |
| Ann Arbor, MI 48109 |
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The connections between neurons are not fixed from birth. On the contrary, they undergo continuous remodeling, especially during postnatal development, but also in adult life. Synaptic plasticity is crucial for the correct functioning of the brain because it allows neurons to re-adjust their connectivity in an activity-dependent manner.
Recent work in my lab has demonstrated that synaptic delivery of neurotransmitter receptors belonging to the AMPA class of glutamate receptors is a crucial element of hippocampal development and synaptic plasticity. Our current research work addresses the following specific projects: 1) Identification of the signal transduction pathways that mediate synaptic delivery, 2) Identification of the cellular machinery that controls the movement and targeting of the receptors, and 3) Structure-function analysis of the AMPA receptor domains that control synaptic delivery.
The major experimental approach is the expression of recombinant proteins in organotypic hippocampal slices using electrophysiology and neuronal imaging as functional assays. We believe this multidisciplinary experimental approach is essential for the general goal of understanding how individual molecules contribute to neuronal function.
Greger I, Esteban JA. AMPA receptor biogenesis and trafficking. Current Opinion in Neurobiology, 2007 Apr 30; [Epub ahead of print].
Gerges NZ, Backos DS, Rupasinghe CN, Spaller MR, Esteban JA. Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane. EMBO Journal 25, 1623-1634 (2006).
Gerges NZ, Brown TC, Correia SS, Esteban JA. Analysis of Rab protein function in neurotransmitter receptor trafficking at hippocampal synapses. Methods in Enzymology 403, 153-166 (2005).
Brown TC, Tran IC, Backos DS, Esteban JA. NMDA receptor-dependent activation of the small GTPase Rab5 drives the removal of synaptic AMPA receptors during hippocampal LTD. Neuron 45, 81-94 (2005).
Gerges NZ, Backos DS, Esteban JA. Local control of AMPA receptor trafficking at the postsynaptic terminal by a small GTPase of the Rab family. Journal of Biological Chemistry 279, 43870-43878 (2004).
Gerges NZ, Tran IC, Backos DS, Harrell JM, Chinkers M, Pratt WB, Esteban JA. Independent functions of Hsp90 in neurotransmitter release and in the continuous synaptic cycling of AMPA receptors. Journal of Neuroscience 24, 4758-4766 (2004).
Esteban JA. AMPA Receptor Trafficking: A Road Map for Synaptic Plasticity. Molecular Interventions 3, 375-385 (2003).
Esteban JA, Shi S-H, Wilson C, Nuriya M, Huganir RL, Malinow R. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Nature Neuroscience 6, 136-143 (2003).
Shi S-H, Hayashi Y, Esteban JA, Malinow R. Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell 105, 331-343 (2001).
Zhu JJ, Esteban JA, Hayashi Y, Malinow R. Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity. Nature Neuroscience 3, 1098-1106 (2000).
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