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.  Our  labs  specific  interest  lies  in studying   the   cellular   and   molecular   mechanisms   that   regulate   the   trafficking   of neurotransmitter receptors in the central nervous system. Currently, the lab is studying the cellular  and  molecular  mechanisms  that  regulate  the  trafficking  of  (1)  ionotropic glutamate  receptors  and  (2)  metabotropic  glutamate  receptors  (mGluRs).  We employ multidisciplinary approaches ranging from biochemistry and molecular biology to cell biology and imaging to address these questions.

For more information about our lab and research please visit Jit’s lab
 

• Ishier Raote, Samarjit Bhattacharyya & Mitradas M Panicker. Functional Selectivity in Serotonin Receptor 2A (5- HT2A) Endocytosis, Recycling and Phosphorylation. Molecular Pharmacology, 83(1): 42-50, 2013.
• Rishi Raj Trivedi & Samarjit Bhattacharyya. Constitutive internalization and recycling of metabotropic glutamate receptor 5 (mGluR5). Biochem Biophys Res Commun. 427(1): 185-190, 2012.
• Citri, A.,* Bhattacharyya, S.,* Ma, C., Morishita, W., Fang, S., Rizo, J., & Malenka, R.C. Calcium binding to PICK1 is essential   for   the   intracellular   retention   of  AMPA  receptors   underlying   long-term   depression.   Journal   of Neuroscience, 30(49): 16437-52, 2010. (* Joint first authors)
• Citri, A., Soler-Llavina, G., Bhattacharyya, S., & Malenka, R. C. N-methyl- Daspartate receptor and metabotropic glutamate receptor-dependent long-term depression are differentially regulated by the ubiquitin-proteasome system. European Journal of Neuroscience, 30(8):1443-50, 2009.
• Bhattacharyya, S., Biou, V., Xu, W., Schlüter, O., & Malenka, R. C. A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nature Neuroscience, 12(2):172-81, 2009.
• Biou, V., Bhattacharyya, S., & Malenka, R. C. Endocytosis and recycling of AMPA receptors lacking GluR2/3. Proc. Natl. Acad. Sci, USA, 105(3):1038-43, 2008.
• Bhattacharyya, S., Raote, I., Bhattacharya, A., Miledi, R., & Panicker, M. M. Activation, internalization, and recycling of the serotonin 2A receptor by dopamine. Proc. Natl. Acad. Sci, USA, 103(41):15248-53. 2006.
• Bhattacharyya, S., Puri, S., Miledi, R., & Panicker, M. M. Internalization and recycling of 5-HT2A receptors activated by serotonin and protein kinase C mediated mechanisms. Proc. Natl. Acad. Sci, USA, 99(22):14470-5, 2002.

Patent: A novel assay for screening antipsychotic drugs. Mitradas. M. Panicker and Samarjit Bhattacharyya.

United States Patent Number: 7524639. European patent approved.