First slide

Research Interests

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.

Selected Publications

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.

No data Found....

No data Found.... No data Found.... No data Found.... No data Found.... No data Found....No data Found.... No data Found.... No data Found.... No data Found.... No data Found....

Publications

TitleJournalYear
Optineurin promotes autophagosome formation by recruiting the autophagy-related Atg12-5-16L1 complex to phagophores containing the Wipi2 protein. J Biol Chem. 293, 132-147. 2018
Altered functions and interactions of glaucoma-associated mutants of optineurin. Frontiers in Immunology 9, 1287. 2018
Autophagy receptor optineurin promotes autophagosome formation by potentiating LC3-II production and phagophore maturation. Commun Integr Biol. 11, 1-4. 2018
Identification of a splice variant of optineurin which is defective in autophagy and phosphorylation. BBA-Mol. Cell Res.1865, 1526-1538. 2018
A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death. Biol Chem. 292(4):1218-1230, 2017. 2017
661W is a retinal ganglion precursor-like cell line in which glaucoma-associated optineurin mutants induce cell death selectively. Sci Rep. 7(1):16855. 2017
Defects in autophagy caused by glaucoma-associated mutations in optineurin. Exp Eye Res.144, 54-63. 2016
The Nobel Prize for understanding autophagy, a cellular mechanism of waste disposal that keeps us healthy. J Biosci. 41(4):563-567 2016
Functional analysis of optineurin and some of its disease-associated mutants. IUBMB Life. 2015 Feb;67(2):120-128. 2015
A glaucoma-associated variant of optineurin, M98K, activates Tbk1 to enhance autophagosome formation and retinal cell death dependent on Ser177 phosphorylation of optineurin. PLoS One 2015 Sep 16;10(9):e0138289. doi: 10.1371/journal.pone.0138289. 2015
E50K-OPTN-induced retinal cell death involves the Rab GTPase-activating protein, TBC1D17 mediated block in autophagy. PLoS One, 2014 Apr 21; 9(4): e95758. 2014
A cataract-causing connexin-50 mutant is mislocalized to the ER due to loss of the fourth transmembrane domain and cytoplasmic domain. FEBS Open Bio. 3, 22-29. 2013
M98K-OPTN induces transferrin receptor degradation and RAB12-mediated autophagic death in retinal ganglion cells. Autophagy 9:4, 510-527. 2013
IRF-1-binding site in the first intron mediates interferon-?-induced optineurin promoter activation. Biochem Biophys Res Commun. 437, 179-184. 2013
Emerging role of tyrosine phosphatase, TCPTP, in the organelles of the early secretory pathway. BBA-Molecular Cell Res. 1833, 1125-1132. 2013
Tyrosine phosphorylation of a SNARE protein, Syntaxin 17: Implications for membrane trafficking in the early secretory pathway. BBA-Molecular Cell Res. 1823, 2109-2119. 2012
Optineurin mediates negative regulation of Rab8 by the GTPase activating protein TBC1D17. J. Cell Science 125, 5026-5039. 2012
Syntaxin 17 cycles between the ER and ERGIC and is required to maintain the architecture of ERGIC and Golgi. Biol. Cell103, 333-350. 2011
Optineurin is required for CYLD-dependent inhibition of TNFalpha induced NF-kB activation. PLoS ONE 6(3):e17477. 2011
Optineurin, a multifunctional protein involved in glaucoma, amyotrophic lateral sclerosis and antiviral signaling. J. Biosci. 35(4), 501-505. 2010
Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant. BMC Cell Biol. 11: 4. 2010
Interaction with Sug1 enables Ipaf ubiquitination leading to caspase-8 activation and cell death. Biochem. J. 427, 91-104. 2010
Opineurin and its mutants: molecules associated with some forms of glaucoma. Ophthalmic Res. 42,176-184. 2009
NF-kB mediates tumor necrosis factor a-induced expression of optineurin, a negative regulator of NF-kB. PLoS ONE 4(4):e5114. 2009
Sp1-like sequences mediate human caspase-3 promoter activation by p73 and cisplatin. FEBS J. 275, 2200-2213. 2008
Focus on Molecules: Optineurin. Experimental Eye Research 87, 1-2. 2008
Tumor necrosis factor a-induced caspase-1 gene expression. Role of p73. FEBS Journal 274, 4396-4407. 2007
Regulation of p73 by Hck through kinase-dependent and independent mechanisms. BMC. Mol. Biol. 8, 45. 2007
C3G is required for c-Abl-induced filopodia and its overexpression promotes filopodia formation. Exp. Cell Res. 313, 2476-2492. 2007
A glaucoma-associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. Invest. Ophthalmol. Vis Sci. 48, 1607-1614. 2007
Involvement of caspase 1 and its activator Ipaf upstream of mitochondrial events in apoptosis. FEBS J. 273, 2766-2778. 2006
Evidence for a role of transmembrane protein p25 in localization of protein tyrosine phosphatase TC48 to the ER. J. Cell Sci. 119, 1703-1714. 2006
Role of p73 in regulating human caspase-1 gene transcription induced by interferon-{gamma} and cisplatin. J. Biol. Chem. 280, 36664-36673. 2005
Caspase-1 activator Ipaf is a p53 inducible gene involved in apoptosis. Oncogene 24, 627-636. 2005
How to design a highly effective siRNA. J. Biosci. 29,129-131. 2004
Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and SFKs localizes to the Golgi and subcortical actin cytoskeleton. BMC Cell Biol. 5, 31. 2004
Physical and functional interaction between Hck tyrosine kinase & guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain. J. Biol. Chem. 278, 52188-52194. 2003
A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis. FEBS Letters, 532, 61-66. 2002
Induction of cytochrome c release and apoptosis by Hck-SH3 domain-mediated signaling requires caspase-3. Apoptosis, 7, 195-212. 2002
Inhibition of anchorage independent cell growth, adhesion and cyclin D1 gene expression by a dominant negative mutant of a tyrosine phosphatase. Experimental Cell Research, 270, 32-44. 2001
Direct transcriptional activation of human caspase-1 by tumor suppressor p53. J. Biol. Chem. 276, 10585-10588. 2001
Nuclear Matrix : Methods of Preparation. Encyclopedia of Life Sciences., A2708: 1-3 (2001). 2001
A nuclear protein tyrosine phosphatase induces shortening of G1 phase and increase in c-Myc protein level. Experimental Cell Research, 265, 1-10. 2001

Ghansyam Swarup

J C Bose Fellow

2616

gshyam@ccmb.res.in

Swetha Medchalmi

SERB National Post-Doctoral Fellow

2648

mswetha@ccmb.res.in

Akhouri Kishore Raghawan

Senior Research Fellow

2648

akraghawan@ccmb.res.in

Shivaranjani C Moharir

Senior Research Fellow

2615

shivranjani@ccmb.res.in

Zuber Wasim Sayyad

Senior Research Fellow

2648

zuberwasim@ccmb.res.in

Rajashree Ramaswamy

Project Assistant

2648