Assistant Professor, Dominick P. Purpura Department of Neuroscience
Molecular mechanisms of metabotropic glutamate receptor trafficking and signaling
Research in the laboratory focuses on elucidating the molecular and cellular underpinnings of metabotropic glutamatergic neurotransmission in the brain, with the ultimate goal of developing a molecular rationale for targeted interventions in neuropsychiatric disorders. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors enriched at excitatory synapses throughout the brain where they act to regulate glutamate-dependent neurotransmission. Signaling by mGluRs is critical to synaptic circuitry formation during development and to forms of activity-dependent synaptic plasticity. Dysregulation of mGluR signaling is implicated in neurological and psychiatric disorders linked to abnormal neurodevelopment, including schizophrenia and Fragile X syndrome, the most common inherited form of intellectual disability.
We use a combination of molecular biology, biochemistry and imaging techniques to uncover the molecular mechanisms underlying temporo-spatial regulation of mGluR signaling and to examine mGluR functions in neuronal homeostasis and synaptic transmission. Ongoing studies pursue two interrelated lines of investigation by examining the role of adaptor proteins in orchestrating and fine-tuning mGluR activity under physiological conditions and in animal models of Fragile X syndrome; and by investigating the mechanisms by which mGluR signaling contributes to synaptogenesis and neuronal maturation.
Kumari, R., and A. Francesconi. (2011). Identification of GPCR localization in Detergent-Resistant Membranes. Methods Mol. Biol. 746:411-423.
Takayasu, Y., Takeuchi, K., Kumari, R., Bennett, M.V., Zukin, R.S., and A. Francesconi. (2010) Caveolin-1 knockout mice exhibit impaired induction of mGluR-dependent long-term depression at CA3-CA1 synapses. Proc. Natl. Acad. Sci. U S A. 107:21778-83.
Francesconi, A., Kumari, R. and R.S. Zukin. (2009). Proteomic analysis reveals novel binding partners of metabotropic glutamatereceptor 1. J. Neurochem. 108:1515-1525.
Francesconi, A., Kumari, R. and R.S. Zukin. (2009). Regulation of group I mGluR trafficking and signaling by the caveolar/lipid raft pathway. J. Neurosci. 29:3590-3602.
Francesconi, A., and Duvoisin, R.M. (2004). Divalent cations modulate the activity of metabotropic glutamate receptors. J. Neurosci. Res. 75, 472-479.
Francesconi, A., and Duvoisin, R. M. (2002). Alternative splicing unmasks dendritic and axonal targeting signals in mGluR1. J. Neurosci. 22, 2196-2205.
Francesconi, A., and Duvoisin, R.M. (2000). Opposing effects of PKC and PKA on metabotropic glutamate receptor signaling. Selective desensitization of the InsP/Ca2+ pathway by phosphorylation of the receptor-G protein coupling domain. Proc. Natl. Acad. Sci. USA 97, 6185-6190.
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Albert Einstein College of Medicine
Rose F. Kennedy Center
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