Head and neck cancer (HNC) is among the ten leading malignancies worldwide, with India solely con... more Head and neck cancer (HNC) is among the ten leading malignancies worldwide, with India solely contributing one-third of global oral cancer cases. The current focus of all cutting-edge strategies against this global malignancy are directed towards the heterogeneous tumor microenvironment that obstructs most treatment blueprints. Subsequent to the portrayal of established information, the review details the application of single cell technology, organoids and spheroid technology in relevance to head and neck cancer and the tumor microenvironment acknowledging the resistance pattern of the heterogeneous cell population in HNC. Bioinformatic tools are used for study of differentially expressed genes and further omics data analysis. However, these tools have several challenges and limitations when analyzing single-cell gene expression data that are discussed briefly. The review further examines the omics of HNC, through comprehensive analyses of genomics, transcriptomics, proteomics, met...
Interest in microbial rhodopsins with ion pumping activity has been revitalized in the context of... more Interest in microbial rhodopsins with ion pumping activity has been revitalized in the context of optogenetics, where light-driven ion pumps are used for cell hyperpolarization and voltage sensing. We identified an opsin-encoding gene (CsR) in the genome of the arctic alga Coccomyxa subellipsoidea C-169 that can produce large photocurrents in Xenopus oocytes. We used this property to analyze the function of individual residues in proton pumping. Modification of the highly conserved proton shuttling residue R83 or its interaction partner Y57 strongly reduced pumping power. Moreover, this mutation converted CsR at moderate electrochemical load into an operational proton channel with inward or outward rectification depending on the amino acid substitution. Together with molecular dynamics simulations, these data demonstrate that CsR-R83 and its interacting partner Y57 in conjunction with water molecules forms a proton shuttle that blocks passive proton flux during the dark-state but pr...
Channelrhodopsins (ChRs) are light-gated ion channels extensively applied as optogenetics tools f... more Channelrhodopsins (ChRs) are light-gated ion channels extensively applied as optogenetics tools for manipulating neuronal activity. All currently known ChRs comprise a large cytoplasmic domain, whose function is elusive. Here, we report the cation channel properties of KnChR, one of the photoreceptors from a filamentous terrestrial alga Klebsormidium nitens, and demonstrate that the cytoplasmic domain of KnChR modulates the ion channel properties. KnChR is constituted of a 7-transmembrane domain forming a channel pore, followed by a C-terminus moiety encoding a peptidoglycan binding domain (FimV). Notably, the channel closure rate was affected by the C-terminus moiety. Truncation of the moiety to various lengths prolonged the channel open lifetime by more than 10-fold. Two Arginine residues (R287 and R291) are crucial for altering the photocurrent kinetics. We propose that electrostatic interaction between the rhodopsin domain and the C-terminus domain accelerates the channel kineti...
Transposition of insertion sequences (IS) is an enzyme-mediated process that only occurs in a min... more Transposition of insertion sequences (IS) is an enzyme-mediated process that only occurs in a minority of cells within a bacterial culture. Transposition is thus a rare event, but transposition frequency may vary depending on experimental conditions. For instance in a rich broth, IS elements are known to transpose during stationary phase but not during exponential growth. Using a reporter system which involves the activation of the cryptic bgl operon in Escherichia coli, we show that the frequency of IS1 transposition is a function of glucose concentration in the growth medium, it is increased by streptomycin amounts that are below minimum inhibitory concentration (sub-MIC) and is inhibited in an rpsL150 strain with high translation accuracy. Since starved cells are known to enhance ribosome frameshifting, our data suggests that growth conditions applied in this study could affect IS1 transposition by increasing translation infidelity.
Translocation of channelrhodopsins (ChRs) is mediated by intraflagellar transport (IFT) machinery... more Translocation of channelrhodopsins (ChRs) is mediated by intraflagellar transport (IFT) machinery. However, the functional role of the network containing photoreceptors, IFT and other proteins in controlling cilia motility of the alga is still not fully delineated. In the current study, we identified two important motifs at the C-terminus of ChR1. One of them is similar to a known ciliary targeting sequence that specifically interacts with a small GTPase, and the other is a SUMOylation site. For the first time, experimental data provide an insight into the role of SUMOylation in the modulation of IFT & ChR1. Blocking of SUMOylation affected the phototaxis of C. reinhardtii cells. This implies SUMOylation based regulation of protein network controlling photomotility. The conservation of SUMOylation site pattern as analyzed for the relevant photoreceptors, IFT and its associated signaling proteins in other ciliated green algae suggested SUMOylation based photobehavioural response acro...
Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fit... more Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fitness. The concerted action of ciliary movement on the respiratory epithelial surface and the pathogen entrapment function of mucus help to maintain healthy airways. Consequently, genetic or acquired defects in lung defense elicit respiratory diseases and secondary microbial infections that inflict damage on pulmonary function and may even be fatal. Individuals living with chronic and acute respiratory diseases are more susceptible to develop severe coronavirus disease-19 (COVID-19) illness and hence should be proficiently managed. In light of the prevailing pandemic, we review the current understanding of the respiratory system and its molecular components with a major focus on the pathophysiology arising due to collapsed respiratory epithelium integrity such as abnormal ciliary movement, cilia loss and dysfunction, ciliated cell destruction, and changes in mucus rheology. The review inc...
Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by sys... more Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by systematic divisions. Metazoans attain structural complexity with exquisite precision, which is a molecular mystery. The indispensable role of centrioles in cell division and ciliogenesis can shed insight into this riddle. Cell division helps in growth of the body and is a highly regulated and integrated process. Its errors cause malignancies. The cell mass is organized during organogenesis. Prior to it, the centrioles are retrieved from the cell cycle to initiate ciliogenesis. The cilia-modulated developmental signaling pathways elaborate the body plan. The secluded compartment of the cilium reduces noise during signaling and is essential for a precise body plan development. The dysfunctional centrioles and cilia can distort body plan. Thus, centriole has a dual role in growth and cellular organization. This concept review analyses the comprehensive interactome and the key domain features ...
Channelrhodopsins are a family of microbial rhodopsins that function as a light-gated ion channel... more Channelrhodopsins are a family of microbial rhodopsins that function as a light-gated ion channel. We report the molecular properties of a novel channelrhodopsin KnRh3 from an evolutionary important filamentous terrestrial alga Klebsormidium nitens. KnRh3 is constituted of a 7-transmembrane domain, followed by a long C-terminus moiety that encodes a peptidoglycan binding domain (FimV). When functionally expressed in mammalian cells, KnRh3 showed light-induced cation channel currents. The maximum action spectrum exhibited was at 430 nm and 460 nm, the former making KnRh3 one of the most blue-shifted channelrhodopsins characterized thus far. The channel closure rate was relatively fast (τ0ff = 10 ms). Surprisingly, photocurrent kinetics were affected by the C-terminus moiety of KnRh3. When this moiety was truncated to various lengths, this prolonged the channel open lifetime by more than 10-fold. We identified two arginine residues, R287 and R291, those are crucial for altering the ki...
Background: Phospholipase C (PLC) is an enzyme that plays pivotal role in a number of signaling c... more Background: Phospholipase C (PLC) is an enzyme that plays pivotal role in a number of signaling cascades. These are active in the plasma membrane and triggers cellular responses by catalyzing the hydrolysis of membrane phospholipids and thereby generating the secondary messengers. Phosphatidylinositol-PLC (PI-PLC) specifically interacts with phosphoino-sitide and/or phosphoinositol and catalyzes specific cleavage of sn-3- phosphodiester bond. Several isoforms of PLC are known to form and function as dimer but very little is known about the molecular basis of the dimerization and its importance in the lipid interaction. Principal Findings: We herein report that, the disruption of disulphide bond of a novel PI-specific PLC of C. reinhardtii (CrPLC) can modulate its interaction affinity with a set of phospholipids and also the stability of its dimer. CrPLC was found to form a mixture of higher oligomeric states with monomer and dimer as major species. Dimer adduct of CrPLC disappeared ...
Blue light sensors using FAD (BLUF) domains are flavin based blue light photoreceptors. The BLUF ... more Blue light sensors using FAD (BLUF) domains are flavin based blue light photoreceptors. The BLUF domains are often fused with various effector domains. BLUF domain coupled with adenylyl cyclase domain is known as photoactivated adenylyl cyclase (PAC). Naegleria gruberi genome database analysis revealed the presence of four PACs. Each of the photoactivated adenylyl cyclases from Naegleria gruberi (NgPACs) is composed of a BLUF domain and an adenylyl cyclase domain. Light regulated enzymatic activity of recombinant NgPAC1 protein was assayed in dark and after blue light irradiation by measuring the cAMP level. Experimental results showed that the NgPAC1 protein exhibits light regulated cyclase activity. In this report, we have also demonstrated that the recombinant NgPAC1 exits as an oligomer in solution.
Head and neck cancer (HNC) is among the ten leading malignancies worldwide, with India solely con... more Head and neck cancer (HNC) is among the ten leading malignancies worldwide, with India solely contributing one-third of global oral cancer cases. The current focus of all cutting-edge strategies against this global malignancy are directed towards the heterogeneous tumor microenvironment that obstructs most treatment blueprints. Subsequent to the portrayal of established information, the review details the application of single cell technology, organoids and spheroid technology in relevance to head and neck cancer and the tumor microenvironment acknowledging the resistance pattern of the heterogeneous cell population in HNC. Bioinformatic tools are used for study of differentially expressed genes and further omics data analysis. However, these tools have several challenges and limitations when analyzing single-cell gene expression data that are discussed briefly. The review further examines the omics of HNC, through comprehensive analyses of genomics, transcriptomics, proteomics, met...
Interest in microbial rhodopsins with ion pumping activity has been revitalized in the context of... more Interest in microbial rhodopsins with ion pumping activity has been revitalized in the context of optogenetics, where light-driven ion pumps are used for cell hyperpolarization and voltage sensing. We identified an opsin-encoding gene (CsR) in the genome of the arctic alga Coccomyxa subellipsoidea C-169 that can produce large photocurrents in Xenopus oocytes. We used this property to analyze the function of individual residues in proton pumping. Modification of the highly conserved proton shuttling residue R83 or its interaction partner Y57 strongly reduced pumping power. Moreover, this mutation converted CsR at moderate electrochemical load into an operational proton channel with inward or outward rectification depending on the amino acid substitution. Together with molecular dynamics simulations, these data demonstrate that CsR-R83 and its interacting partner Y57 in conjunction with water molecules forms a proton shuttle that blocks passive proton flux during the dark-state but pr...
Channelrhodopsins (ChRs) are light-gated ion channels extensively applied as optogenetics tools f... more Channelrhodopsins (ChRs) are light-gated ion channels extensively applied as optogenetics tools for manipulating neuronal activity. All currently known ChRs comprise a large cytoplasmic domain, whose function is elusive. Here, we report the cation channel properties of KnChR, one of the photoreceptors from a filamentous terrestrial alga Klebsormidium nitens, and demonstrate that the cytoplasmic domain of KnChR modulates the ion channel properties. KnChR is constituted of a 7-transmembrane domain forming a channel pore, followed by a C-terminus moiety encoding a peptidoglycan binding domain (FimV). Notably, the channel closure rate was affected by the C-terminus moiety. Truncation of the moiety to various lengths prolonged the channel open lifetime by more than 10-fold. Two Arginine residues (R287 and R291) are crucial for altering the photocurrent kinetics. We propose that electrostatic interaction between the rhodopsin domain and the C-terminus domain accelerates the channel kineti...
Transposition of insertion sequences (IS) is an enzyme-mediated process that only occurs in a min... more Transposition of insertion sequences (IS) is an enzyme-mediated process that only occurs in a minority of cells within a bacterial culture. Transposition is thus a rare event, but transposition frequency may vary depending on experimental conditions. For instance in a rich broth, IS elements are known to transpose during stationary phase but not during exponential growth. Using a reporter system which involves the activation of the cryptic bgl operon in Escherichia coli, we show that the frequency of IS1 transposition is a function of glucose concentration in the growth medium, it is increased by streptomycin amounts that are below minimum inhibitory concentration (sub-MIC) and is inhibited in an rpsL150 strain with high translation accuracy. Since starved cells are known to enhance ribosome frameshifting, our data suggests that growth conditions applied in this study could affect IS1 transposition by increasing translation infidelity.
Translocation of channelrhodopsins (ChRs) is mediated by intraflagellar transport (IFT) machinery... more Translocation of channelrhodopsins (ChRs) is mediated by intraflagellar transport (IFT) machinery. However, the functional role of the network containing photoreceptors, IFT and other proteins in controlling cilia motility of the alga is still not fully delineated. In the current study, we identified two important motifs at the C-terminus of ChR1. One of them is similar to a known ciliary targeting sequence that specifically interacts with a small GTPase, and the other is a SUMOylation site. For the first time, experimental data provide an insight into the role of SUMOylation in the modulation of IFT & ChR1. Blocking of SUMOylation affected the phototaxis of C. reinhardtii cells. This implies SUMOylation based regulation of protein network controlling photomotility. The conservation of SUMOylation site pattern as analyzed for the relevant photoreceptors, IFT and its associated signaling proteins in other ciliated green algae suggested SUMOylation based photobehavioural response acro...
Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fit... more Mucociliary defense, mediated by the ciliated and goblet cells, is fundamental to respiratory fitness. The concerted action of ciliary movement on the respiratory epithelial surface and the pathogen entrapment function of mucus help to maintain healthy airways. Consequently, genetic or acquired defects in lung defense elicit respiratory diseases and secondary microbial infections that inflict damage on pulmonary function and may even be fatal. Individuals living with chronic and acute respiratory diseases are more susceptible to develop severe coronavirus disease-19 (COVID-19) illness and hence should be proficiently managed. In light of the prevailing pandemic, we review the current understanding of the respiratory system and its molecular components with a major focus on the pathophysiology arising due to collapsed respiratory epithelium integrity such as abnormal ciliary movement, cilia loss and dysfunction, ciliated cell destruction, and changes in mucus rheology. The review inc...
Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by sys... more Metazoans have an elaborate and functionally segmented body. It evolves from a single cell by systematic divisions. Metazoans attain structural complexity with exquisite precision, which is a molecular mystery. The indispensable role of centrioles in cell division and ciliogenesis can shed insight into this riddle. Cell division helps in growth of the body and is a highly regulated and integrated process. Its errors cause malignancies. The cell mass is organized during organogenesis. Prior to it, the centrioles are retrieved from the cell cycle to initiate ciliogenesis. The cilia-modulated developmental signaling pathways elaborate the body plan. The secluded compartment of the cilium reduces noise during signaling and is essential for a precise body plan development. The dysfunctional centrioles and cilia can distort body plan. Thus, centriole has a dual role in growth and cellular organization. This concept review analyses the comprehensive interactome and the key domain features ...
Channelrhodopsins are a family of microbial rhodopsins that function as a light-gated ion channel... more Channelrhodopsins are a family of microbial rhodopsins that function as a light-gated ion channel. We report the molecular properties of a novel channelrhodopsin KnRh3 from an evolutionary important filamentous terrestrial alga Klebsormidium nitens. KnRh3 is constituted of a 7-transmembrane domain, followed by a long C-terminus moiety that encodes a peptidoglycan binding domain (FimV). When functionally expressed in mammalian cells, KnRh3 showed light-induced cation channel currents. The maximum action spectrum exhibited was at 430 nm and 460 nm, the former making KnRh3 one of the most blue-shifted channelrhodopsins characterized thus far. The channel closure rate was relatively fast (τ0ff = 10 ms). Surprisingly, photocurrent kinetics were affected by the C-terminus moiety of KnRh3. When this moiety was truncated to various lengths, this prolonged the channel open lifetime by more than 10-fold. We identified two arginine residues, R287 and R291, those are crucial for altering the ki...
Background: Phospholipase C (PLC) is an enzyme that plays pivotal role in a number of signaling c... more Background: Phospholipase C (PLC) is an enzyme that plays pivotal role in a number of signaling cascades. These are active in the plasma membrane and triggers cellular responses by catalyzing the hydrolysis of membrane phospholipids and thereby generating the secondary messengers. Phosphatidylinositol-PLC (PI-PLC) specifically interacts with phosphoino-sitide and/or phosphoinositol and catalyzes specific cleavage of sn-3- phosphodiester bond. Several isoforms of PLC are known to form and function as dimer but very little is known about the molecular basis of the dimerization and its importance in the lipid interaction. Principal Findings: We herein report that, the disruption of disulphide bond of a novel PI-specific PLC of C. reinhardtii (CrPLC) can modulate its interaction affinity with a set of phospholipids and also the stability of its dimer. CrPLC was found to form a mixture of higher oligomeric states with monomer and dimer as major species. Dimer adduct of CrPLC disappeared ...
Blue light sensors using FAD (BLUF) domains are flavin based blue light photoreceptors. The BLUF ... more Blue light sensors using FAD (BLUF) domains are flavin based blue light photoreceptors. The BLUF domains are often fused with various effector domains. BLUF domain coupled with adenylyl cyclase domain is known as photoactivated adenylyl cyclase (PAC). Naegleria gruberi genome database analysis revealed the presence of four PACs. Each of the photoactivated adenylyl cyclases from Naegleria gruberi (NgPACs) is composed of a BLUF domain and an adenylyl cyclase domain. Light regulated enzymatic activity of recombinant NgPAC1 protein was assayed in dark and after blue light irradiation by measuring the cAMP level. Experimental results showed that the NgPAC1 protein exhibits light regulated cyclase activity. In this report, we have also demonstrated that the recombinant NgPAC1 exits as an oligomer in solution.
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Papers by Suneel Kateriya