The central theme of my group`s research is to understand the function of the protein optineurin and to study the functional defects caused by disease-associated mutations in optineurin. Mutations in the coding region of the gene OPTN, which codes for the protein optineurin, cause glaucoma and ALS (amyotrophic lateral sclerosis). Both of these are neurodegenerative diseases. In glaucoma, the loss of vision is irreversible, which occurs due to progressive degeneration of retinal ganglion cells in the optic nerve head. ALS is a fatal progressive disease, which involves degeneration of motor neurons of the primary cortex, brainstem and spinal cord. Optineurin is also seen in pathological structures present in Alzheimer`s disease and Parkinson`s disease. The role of optineurin and its mutants in regulating autophagy, membrane vesicle trafficking, signalling, stress response and gene expression is being investigated.
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- Bansal M, Moharir SC, Sailasree SP, Sirohi K, Sudhakar C, Sarathi DP, Lakshmi BJ, Buono M, Kumar S, Swarup G. Optineurin promotes autophagosome formation by recruiting the autophagy-related Atg12-5-16L1 complex to phagophores containing the Wipi2 protein. J Biol Chem. 2018, 293, 132-147.
- Swarup, G., Sayyad, Z. Altered functions and interactions of glaucoma-associated mutants of optineurin. Frontiers in Immunology 2018, 9, 1287.
- Raghawan, A. K., Sripada, A., Gopinath, G., Pushpanjali, P., Kumar, Y., Radha, V., Swarup, G. A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death. J Biol Chem. 2017, 292(4):1218-1230.
- Sirohi K, Chalasani ML, Sudhakar C, Kumari A, Radha V, Swarup G. (2013) M98K-OPTN induces transferrin receptor degradation and RAB12-mediated autophagic death in retinal ganglion cells. Autophagy 9:4, 510-527.
- V. Vaibhava, A. Nagabhushana, M.L.S. Chalasani, C. Sudhakar, A. Kumari and G. Swarup (2012). Optineurin mediates a negative regulation of Rab8 by the GTPase activating protein TBC1D17. J. Cell Science 125, 5026-5039.
- A. Nagabhushana, M.L. Chalasani, N. Jain, V Radha, N. Rangaraj, D. Balasubramanian and G. Swarup (2010). Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant. BMC Cell Biol. 11: 4.