Receptor Guanylyl Cyclase C (GC-C)
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Postdoctoral positions are available to work in the general area of gut physiology using mouse models. Studies will focus on the use of organoids, gut-associated microbiome, and understanding molecular mechanisms that underlie colorectal tumourogenesis. Individuals with an interest in human genetics and characterising variants identified by exome sequencing are encouraged to apply. Please contact Prof. Visweswariah by email (sandhya@iisc.ac.in), enclosing a detailed CV and research interests.
Signalling mediated via GC-C
Signalling mediated via GC-C
GC-C (product of the GUCY2c gene in humans) is the target of bacterial heat-stable enterotoxins that cause watery diarrhoea in children and travellers to middle and low income countries. This receptor has a complex topology consisting of an extracellular ligand binding domain, an intracellular kinase homology domain, and a C-terminal guanyly cyclase domain. Activation of the receptor results in intracellular cGMP accumulation, that triggers a whole host of signaling cascades in the intestinal cell, ultimately leading to ion and water efflux.
GC-C (product of the GUCY2c gene in humans) is the target of bacterial heat-stable enterotoxins that cause watery diarrhoea in children and travellers to middle and low income countries. This receptor has a complex topology consisting of an extracellular ligand binding domain, an intracellular kinase homology domain, and a C-terminal guanyly cyclase domain. Activation of the receptor results in intracellular cGMP accumulation, that triggers a whole host of signaling cascades in the intestinal cell, ultimately leading to ion and water efflux.
We have been interested in studying aspects of receptor structure and regulation using mutational analysis and heterologous expression of various receptor domains. We have utilized mouse models to study the role of this receptor in intestinal cell proliferation and infection. Working with collaborators around the world, we have identified mutations in GUCY2c that cause human disease. We are currently developing transgenic mouse models to further understand molecular regulation of GC-C action in the mammalian gut.
We have been interested in studying aspects of receptor structure and regulation using mutational analysis and heterologous expression of various receptor domains. We have utilized mouse models to study the role of this receptor in intestinal cell proliferation and infection. Working with collaborators around the world, we have identified mutations in GUCY2c that cause human disease. We are currently developing transgenic mouse models to further understand molecular regulation of GC-C action in the mammalian gut.
Important Publications:
Mishra V., Bose A., Kiran S., Banerjee S., A Shah I., Chaukimath P., M Reshi M., Srinivas S., Barman A., Visweswariah SS. (2021) Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C. J. Exp. Med. doi: 10.1084/jem.20210479.
Mishra V., Bose A., Kiran S., Banerjee S., A Shah I., Chaukimath P., M Reshi M., Srinivas S., Barman A., Visweswariah SS. (2021) Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C. J. Exp. Med. doi: 10.1084/jem.20210479.
Prasad H, Visweswariah SS. (2021) Impaired intestinal sodium transport in inflammatory bowel disease: from the passenger to the driver's seat. Cell Mol. Gastroenterol. Hepatol. doi: 10.1016/j.jcmgh.2021.03.005
Prasad H, Visweswariah SS. (2021) Impaired intestinal sodium transport in inflammatory bowel disease: from the passenger to the driver's seat. Cell Mol. Gastroenterol. Hepatol. doi: 10.1016/j.jcmgh.2021.03.005
Bose A, Banerjee S, Visweswariah SS. (2020) Mutational Landscape of Receptor Guanylyl Cyclase C: Functional Analysis and Disease-Related Mutations. IUBMB Life. doi: 10.1002/iub.2283.
Bose A, Banerjee S, Visweswariah SS. (2020) Mutational Landscape of Receptor Guanylyl Cyclase C: Functional Analysis and Disease-Related Mutations. IUBMB Life. doi: 10.1002/iub.2283.
Prasad H, Shenoy AR, Visweswariah SS. (2019) Cyclic nucleotides, gut physiology and inflammation. FEBS J. doi: 10.1111/febs.15198.
Prasad H, Shenoy AR, Visweswariah SS. (2019) Cyclic nucleotides, gut physiology and inflammation. FEBS J. doi: 10.1111/febs.15198.
Mishra, V., Goel, R. and Visweswariah, S.S. (2018) The kinase homology domain in receptor guanylyl cyclases: nothing ‘pseudo’ about it. Biochem. Soc. Trans. DOI: https://doi.org/10.1042/BST20180472
Mishra, V., Goel, R. and Visweswariah, S.S. (2018) The kinase homology domain in receptor guanylyl cyclases: nothing ‘pseudo’ about it. Biochem. Soc. Trans. DOI: https://doi.org/10.1042/BST20180472
Majumdar, S., Mishra, V., Nandi, S., Abdullah, M., Barman, A., Raghavan, A., Nandi, D. and Visweswariah, S.S. (2018) Absence of receptor guanylyl cyclase C enhances ileal damage and reduces cytokine and antimicrobial peptide production during oral Salmonella Typhimurium infection. Infect. Immun. 86: 799-817
Majumdar, S., Mishra, V., Nandi, S., Abdullah, M., Barman, A., Raghavan, A., Nandi, D. and Visweswariah, S.S. (2018) Absence of receptor guanylyl cyclase C enhances ileal damage and reduces cytokine and antimicrobial peptide production during oral Salmonella Typhimurium infection. Infect. Immun. 86: 799-817
Müller. T., Rasool, I., Heinz-Erian, P., Mildenberger, E., Hülstrunk, C., Müller, A., Michaud, L., Koot, B.G., Ballauff, A., Vodopiutz, J., Rosipal, S., Petersen, B.S., Franke, A., Fuchs, I., Witt, H., Zoller, H., Janecke, A.R. and Visweswariah, S.S. (2016) Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C. Gut. 65: 1306-1313
Müller. T., Rasool, I., Heinz-Erian, P., Mildenberger, E., Hülstrunk, C., Müller, A., Michaud, L., Koot, B.G., Ballauff, A., Vodopiutz, J., Rosipal, S., Petersen, B.S., Franke, A., Fuchs, I., Witt, H., Zoller, H., Janecke, A.R. and Visweswariah, S.S. (2016) Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C. Gut. 65: 1306-1313
Basu, N., Saha, S., Khan, I., Ramachandra, S.S. and Visweswariah, S.S.(2014) Intestinal cell proliferation and senescence is regulated by receptor guanylyl cyclase C and p21. J. Biol. Chem. 289: 581-593.
Basu, N., Saha, S., Khan, I., Ramachandra, S.S. and Visweswariah, S.S.(2014) Intestinal cell proliferation and senescence is regulated by receptor guanylyl cyclase C and p21. J. Biol. Chem. 289: 581-593.
Arshad, N., Ballal, S. and Visweswariah, S.S. (2013) Site-specific N-Linked Glycosylation of Receptor Guanylyl Cyclase C Regulates Ligand Binding, Ligand-mediated Activation and Interaction with Vesicular Integral Membrane Protein 36, VIP36. J. Biol. Chem. 288: 3907-3917.
Arshad, N., Ballal, S. and Visweswariah, S.S. (2013) Site-specific N-Linked Glycosylation of Receptor Guanylyl Cyclase C Regulates Ligand Binding, Ligand-mediated Activation and Interaction with Vesicular Integral Membrane Protein 36, VIP36. J. Biol. Chem. 288: 3907-3917.
Fiskerstrand, T., Arshad, N., Haukanes, B.I., Tronstad, R.R.,§Pham, K.D., Johansson, S., Håvik, B., Tønder, S.L, Levy, S.E., Brackman, D., Boman, H., Biswas, K.H., Apold, J., Hovdenak, N., Visweswariah, S.S.and Knappskog, P.M. (2012) Familial Diarrhea Syndrome caused by an activating GUCY2C activating mutation. N. Engl. J. Med.366: 1586-1595.
Fiskerstrand, T., Arshad, N., Haukanes, B.I., Tronstad, R.R.,§Pham, K.D., Johansson, S., Håvik, B., Tønder, S.L, Levy, S.E., Brackman, D., Boman, H., Biswas, K.H., Apold, J., Hovdenak, N., Visweswariah, S.S.and Knappskog, P.M. (2012) Familial Diarrhea Syndrome caused by an activating GUCY2C activating mutation. N. Engl. J. Med.366: 1586-1595.
Basu, N., Bhandari, R., Tirumlai, V. and Visweswariah, S.S. (2009)Cross-talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis. Mol Cell. Biol. 29: 5277-5289
Basu, N., Bhandari, R., Tirumlai, V. and Visweswariah, S.S. (2009)Cross-talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis. Mol Cell. Biol. 29: 5277-5289
Saha, S., Biswas, K.H., Kondapalli, C., Isloor, N. and Visweswariah, S.S.(2009) The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C (GC-C) J. Biol. Chem. 284: 27135-27145
Saha, S., Biswas, K.H., Kondapalli, C., Isloor, N. and Visweswariah, S.S.(2009) The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C (GC-C) J. Biol. Chem. 284: 27135-27145
Biswas, K.H. and Visweswariah, S.S. (2011) Distinct allostery induced in the cyclic GMP-binding, cGMP-specific phosphodiesterase (PDE5) by cGMP, sildenafil and metal ions. J. Biol. Chem. 286: 8545-8554.
Biswas, K.H. and Visweswariah, S.S. (2011) Distinct allostery induced in the cyclic GMP-binding, cGMP-specific phosphodiesterase (PDE5) by cGMP, sildenafil and metal ions. J. Biol. Chem. 286: 8545-8554.
Biswas, K.H., Shenoy, A.R., Dutta, A. and Visweswariah, S.S.(2009) The evolution of guanylyl cyclases as multidomain proteins: conserved features of kinase-cyclase domain fusions. J. Mol. Evol.68: 587-602
Biswas, K.H., Shenoy, A.R., Dutta, A. and Visweswariah, S.S.(2009) The evolution of guanylyl cyclases as multidomain proteins: conserved features of kinase-cyclase domain fusions. J. Mol. Evol.68: 587-602
Biswas, K.H., Sopory, S. and Visweswariah, S.S.(2008) The GAF domain of the cGMP-binding, cGMP-specific Phosphodiesterase (PDE5) is a sensor and a sink for cGMP. Biochemistry47: 3534-3543
Biswas, K.H., Sopory, S. and Visweswariah, S.S.(2008) The GAF domain of the cGMP-binding, cGMP-specific Phosphodiesterase (PDE5) is a sensor and a sink for cGMP. Biochemistry47: 3534-3543