Cellular and Molecular Mechanisms of Protein Trafficking in the Central Nervous System
An essential requirement for maintenance of homeostasis in any living organism is the ability of cells to sense the external environment and, in the case of multicellular organisms, for cells to communicate with each other via mediators released into the extracellular milieu. In the brain, a variety of neurotransmitters and neuromodulators act on target receptors to activate cellular signaling events which transfer information from one cell to the next. Normal signaling depends on accurate localization of such receptors in specific regions of the cell, and the process of receptor trafficking plays a critical role in controlling this localization. Despite the obvious significance of this process, we still know very little about the protein machineries that mediate trafficking of neurotransmitter receptors in the brain, the regulatory events that control these protein machineries, and the functional consequences of these regulatory events. Research in my laboratory is directed to elucidate the cellular and molecular mechanisms that regulate the trafficking of (a) ionotropic glutamate receptors and (b) G-protein coupled receptors (GPCRs) in the central nervous system. These trafficking events are thought to be critical for various physiological processes. For example, glutamate receptor trafficking is believed to be involved in virtually all forms of experience-dependent plasticity including learning and memory. On the other hand, GPCR trafficking is believed to play crucial role in various physiological processes as well as in various neuropsychiatric disorders. My laboratory would employ multi-disciplinary approaches ranging from biochemistry and molecular biology to cell biology, imaging, and mouse genetics to address these questions.
- Pandey S*, Ramsakha N*, Sharma R, Gulia R, Ojha P, Lu W, Bhattacharyya S. (2020) The post-synaptic scaffolding protein Tamalin regulates ligand-mediated trafficking of metabotropic glutamate receptors. J. Biol. Chem. 295(25):8575-88. (* These authors contributed equally to this work)
- Sharma R*, Gulia R*, Bhattacharyya S. (2019) Analysis of ubiquitination and ligand-dependent trafficking of group I mGluRs. Methods in Cell Biology. 149:107-30. (* These authors contributed equally to this work)
- Mahato PK*, Ramsakha N*, Ojha P*, Gulia R*, Sharma R*, Bhattacharyya S. (2018) Group I Metabotropic Glutamate Receptors (mGluRs): Ins and Outs. Adv Exp Med Biol. 1112:163-75. (* These authors contributed equally to this work)
- Sharma R, Gulia R, Bhattacharyya S. (2018) A critical role for Sorting Nexin 1 in the trafficking of metabotropic glutamate receptors. Journal of Neuroscience. 38(40):8605-20.
- Gulia R, Sharma R, Bhattacharyya S. (2017) A critical role for ubiquitination in the endocytosis of Glutamate receptors. J. Biol. Chem. 292(4), 1426-37.
- Bhattacharyya S. (2016) Inside story of Group I Metabotropic Glutamate Receptors (mGluRs). The International Journal of Biochemistry & Cell Biology. 77(Pt B), 205-12.
- Mahato PK, Pandey S, Bhattacharyya S. (2015) Differential effects of protein phosphatases in the recycling of metabotropic glutamate receptor 5. Neuroscience. 306, 138-50.
- Pandey, S., Mahato, P. K., and Bhattacharyya, S. (2014) Metabotropic glutamate receptor 1 recycles to the cell surface in protein phosphatase 2A-dependent manner in non-neuronal and neuronal cell lines. Journal of Neurochemistry. 131(5), 602-14.
- Trivedi, R. R., and Bhattacharyya, S. (2012) Constitutive internalization and recycling of metabotropic glutamate receptor 5 (mGluR5). Biochemical and Biophysical Research Communications 427, 185-190.
- Bhattacharyya, S., Biou, V., Xu, W., Schluter, O., and Malenka, R. C. (2009) A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nature Neuroscience 12, 172-181.
- Bhattacharyya, S., Raote, I., Bhattacharya, A., Miledi, R., and Panicker, M. M. (2006) Activation, internalization, and recycling of the serotonin 2A receptor by dopamine. Proceedings of the National Academy of Sciences of the United States of America (PNAS) 103, 15248-15253.
- Bhattacharyya, S., Puri, S., Miledi, R., and Panicker, M. M. (2002) Internalization and recycling of 5-HT2A receptors activated by serotonin and protein kinase C-mediated mechanisms. Proceedings of the National Academy of Sciences of the United States of America (PNAS) 99, 14470-14475.