Review
Pathology
Sun-Ji Park, Chuang Li, Ying Maggie Chen
Summary: Maintaining Ca2+ homeostasis is crucial for cellular function and survival, with the endoplasmic reticulum acting as the major intracellular Ca2+ store. Dysregulation of ER Ca2+ homeostasis is associated with various diseases, particularly in kidney diseases, highlighting the importance of ER Ca2+ channels, pumps, and binding proteins. Despite advancements in understanding, treatment for ER Ca2+ imbalance in kidney diseases remains elusive.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Brian S. Mantilla, Leticia D. Do Amaral, Henning J. Jessen, Roberto Docampo
Summary: The study highlights the importance of highly phosphorylated IPs in the life cycle of T. cruzi, identifying new highly phosphorylated IPs and the kinases involved in their synthesis.
ACS CHEMICAL BIOLOGY
(2021)
Article
Cell Biology
Ana M. Rossi, Andrew M. Riley, Genevieve Dupont, Taufiq Rahman, Barry V. L. Potter, Colin W. Taylor
Summary: Inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are intracellular Ca2+ channels linking extracellular stimuli to Ca2+ signals. Research shows that quantal responses to low IP3 concentrations do not require heterogeneous Ca2+ stores, and IP(3)Rs exhibit incremental responses to IP3 stimulation. This suggests that Ca2+ signals evoked by IP3 pulses arise from rapid activation and inactivation of a small fraction of IP(3)Rs.
Article
Multidisciplinary Sciences
Justin Y. Toh, Agathe Nkouawa, Saul Rojas Sanchez, Huafang Shi, Nikolay G. Kolev, Christian Tschudi
Summary: By targeting 86 transcripts through RNAi, 22 genes that positively or negatively regulate the progression towards infectivity in Trypanosoma brucei have been identified, including the previously unknown nucleic acid binding proteins CSD1 and CSD2. The study suggests a considerable overlap between the genes that regulate stumpy bloodstream form Trypanosoma and those that govern the development of metacyclic form parasites.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Lukas Kuester, Themistoklis Paraschiakos, Kader Ebru Karakurt, Udo Schumacher, Bjoern-Philipp Diercks, Sabine Windhorst
Summary: The up-regulation of ITPKA in lung cancer cells is associated with increased migration and invasion, and its actin bundling activity is the main factor controlling this effect.
BIOSCIENCE REPORTS
(2023)
Article
Computer Science, Artificial Intelligence
Randall Clark, Lawson Fuller, Jason A. Platt, Henry D. I. Abarbanel
Summary: This article introduces how to use methods from nonlinear dynamics and interpolation techniques from applied mathematics to construct discrete time dynamical rules that forecast observed neuron properties accurately, which is crucial for the development of neural network models and biological networks.
NEURAL COMPUTATION
(2022)
Article
Biology
Noopur Dave, Ugur Cetiner, Daniel Arroyo, Joshua Fonbuena, Megna Tiwari, Patricia Barrera, Noelia Lander, Andriy Anishkin, Sergei Sukharev, Veronica Jimenez
Summary: A novel mechanosensitive channel, TcMscS, has been identified and characterized in Trypanosoma cruzi, which is activated by membrane tension and forms a large pore permeable to various substances. Knockout parasites of TcMscS exhibit fitness defects, including increased cell volume, calcium dysregulation, impaired differentiation, and a dramatic decrease in infectivity, providing mechanistic insights into pathogen adaptation inside the host.
Article
Cell Biology
Eliane Tihon, Karinna Rubio-Pena, Annick Dujeancourt-Henry, Aline Crouzols, Brice Rotureau, Lucy Glover
Summary: The life cycle of Trypanosoma brucei alternates between the tsetse fly vector and the mammalian host, and the infectivity to the host depends on the expression of metacyclic variant surface glycoprotein genes. This study reveals the role of VEX1 in the metacyclic differentiation process and its impact on the infectivity of T. brucei to mammalian hosts.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Laura Marongiu, Francesca Mingozzi, Clara Cigni, Roberta Marzi, Marco Di Gioia, Massimiliano Garre, Dario Parazzoli, Laura Sironi, Maddalena Collini, Reiko Sakaguchi, Takashi Morii, Mariacristina Crosti, Monica Moro, Stephane Schurmans, Tiziano Catelani, Rany Rotem, Miriam Colombo, Stephen Shears, Davide Prosperi, Ivan Zanoni, Francesca Granucci
Summary: Recognition of LPS by DCs involves the receptor complex CD14 and TLR4, and subsequent Ca2+ mobilization and NFAT activation require IP3R3 and ITPKB. Targeting ITPKB may offer a promising approach for anti-inflammatory therapies aimed at inhibiting specific DC functions.
Article
Biochemistry & Molecular Biology
Lukas Kuester, Themistoklis Paraschiakos, Kader Ebru Karakurt, Udo Schumacher, Bjoern-Philipp Diercks, Sabine Windhorst
Summary: Expression of ITPKA is up-regulated in many tumor types and is associated with bad prognosis in lung cancer cells. It has been shown that high levels of ITPKA increase migration and invasion of lung cancer cell lines. The study demonstrates that the actin bundling activity of ITPKA controls migration and invasion under basal conditions, while the Ins(1,4,5)P-3-kinase activity slightly enhances this effect in the presence of ATP.
BIOSCIENCE REPORTS
(2023)
Article
Physics, Fluids & Plasmas
Irina Bashkirtseva, Lev Ryashko
Summary: The stochastic excitability of spiking oscillatory regimes in calcium kinetics is investigated using the Li-Rinzel conceptual model. The probabilistic mechanisms of noise-induced generation of large-amplitude oscillations in parametric zones are studied numerically and analytically. The phenomenon of coherence resonance is discussed, and a parametric statistical description of interspike intervals is applied. The role of confidence ellipses and separatrices in determining sub- and supercritical regions is demonstrated.
Article
Immunology
Prarthana J. Dalal, David P. Sullivan, Evan W. Weber, David B. Sacks, Matthias Gunzer, Isabella M. Grumbach, Joan Heller Brown, William A. Muller
Summary: The research highlights the important roles of endothelial CaM and CaMKIIδ in transducing specific calcium signals required for TEM, which interferes with the delivery of the lateral border recycling compartment (LBRC) and reduces TEM.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Vikas Arige, Lara E. Terry, Larry E. Wagner, Sundeep Malik, Mariah R. Baker, Guizhen Fan, Suresh K. Joseph, Irina I. Serysheva, David I. Yule
Summary: Inositol 1,4,5-trisphosphate receptors (IP3Rs) initiate physiological responses by regulating intracellular calcium signals. This study identifies Ca2+ binding sites and acidic residues that regulate IP3Rs channel activity, providing insights into their regulatory mechanism.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Anuj Tripathi, Ujjal K. Singha, Ayorinde Cooley, Taneisha Gillyard, Evan Krystofiak, Siddharth Pratap, Jamaine Davis, Minu Chaudhuri
Summary: TbTim50 is essential for mitochondrial function, regulation of kDNA replication, and the cell cycle in the bloodstream form of T. brucei. Depletion of TbTim50 results in inhibited cell growth, changes in morphology, increased AMPK phosphorylation, and upregulation of stumpy marker genes. TbTim50 is a crucial therapeutic target for African trypanosomiasis.
Article
Multidisciplinary Sciences
Roberto Ornelas-Guevara, Diana Gil, Valerie Voorsluijs, Genevieve Dupont
Summary: Inositol 1,4,5-trisphosphate (IP3) plays a key role in calcium signaling. Previous studies overestimated the diffusion coefficient of IP3 in vivo, but new computational analysis shows that the effective diffusion coefficient is close to 100 μm(2)s(-1), significantly lower than previous estimations. This moderate reduction can be explained by the buffering effect of non-fully bound inactive IP3 receptors.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Srinivasan Ramakrishnan, Linn M. Unger, Rodrigo P. Baptista, Teresa Cruz-Bustos, Roberto Docampo
Summary: This study demonstrates that ablation of a Golgi-localized cation transporter in Trypanosoma cruzi prevents normal protein glycosylation, host cell invasion, and intracellular replication, while glycosylation can be rescued by Mn2+ but not by other cations. These findings highlight the crucial role of Mn2+ in host-parasite interaction and protein glycosylation.
Editorial Material
Plant Sciences
Jose R. Perez-Castineira, Roberto Docampo, Tatsuhiro Ezawa, Aurelio Serrano
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Roberto Docampo, Anibal Eugenio Vercesi
Summary: This review discusses the mechanisms of mitochondrial oxidant generation and removal, and the involvement of Ca2+ in trypanosome cell death, highlighting the need for further studies on ROS generation, defense mechanisms, and mitochondrial permeability transition pore in trypanosomatids.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Srinivasan Ramakrishnan, Rodrigo P. Baptista, Beejan Asady, Guozhong Huang, Roberto Docampo
Summary: In Trypanosoma brucei, down-regulation of Vps41 expression through RNAi leads to significant inhibition of endocytosis, affecting cell growth, while other functions of Vps41 in mammalian and yeast cells remain unaffected. The essentiality of TbVps41 suggests it as a potential drug target.
Article
Biochemistry & Molecular Biology
Guilherme Rodrigo R. M. Dos Santos, Ana Catarina Rezende Leite, Noelia Lander, Miguel Angel Chiurillo, Anibal Eugenio Vercesi, Roberto Docampo
Summary: Letm1 is crucial for mitochondrial Ca2+ uptake and release in Trypanosoma cruzi, affecting growth, metabolism, and cell viability.
Review
Microbiology
Roberto Docampo, Silvia N. J. Moreno
Summary: This review examines recent findings in calcium ion signaling in two groups of intracellular protist parasites, the apicomplexan and the trypanosomatid parasites, which may facilitate invasion, respond to environmental changes within the host, or regulate the function of their intracellular organelles.
CURRENT OPINION IN MICROBIOLOGY
(2021)
Article
Microbiology
Fatma Gomaa, Zhu-Hong Li, David J. Beaudoin, Heba Alzan, Peter R. Girguis, Roberto Docampo, Virginia P. Edgcomb
Summary: Developing transfection protocols for marine protists is an emerging field. In this study, we successfully developed a CRISPR/Cas9 editing protocol for Bodo saltans and identified two mechanisms for repairing double-strand breaks in this organism.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Review
Microbiology
Roberto Docampo, Guozhong Huang
Summary: Acidocalcisomes are organelles found in bacteria and eukaryotes. They play important roles in autophagy, ion and phosphorus storage, osmoregulation, pH homeostasis, and pathogenesis. Recent studies have also revealed their involvement in phosphate utilization, calcium ion signaling, and bioenergetics.
JOURNAL OF EUKARYOTIC MICROBIOLOGY
(2022)
Article
Microbiology
Brian S. Mantilla, Cristina Azevedo, Paul W. Denny, Adolfo Saiardi, Roberto Docampo
Summary: This study reveals the crucial role of histidine ammonia lyase (HAL) in the alkalinization of acidocalcisomes by binding to polyphosphate and regulating its function through lysine residues in the C-terminal region. HAL localization and inhibition by polyP demonstrate a mechanism for acidocalcisome alkalinization linked to amino acid metabolism.
Article
Chemistry, Medicinal
Alejandro Pezza, Luis E. Tavernelli, Victoria L. Alonso, Virginia Perdomo, Raquel Gabarro, Rab Prinjha, Elvio Rodriguez Araya, Inmaculada Rioja, Roberto Docampo, Felix Calderon, Julio Martin, Esteban Serra
Summary: TcBDF2 is an important bromodomain protein in T. cruzi, playing a crucial role in infection, replication, and differentiation of the parasite, as well as pathogenesis.
ACS INFECTIOUS DISEASES
(2022)
Article
Cell Biology
Mayara S. Bertolini, Roberto Docampo
Summary: In this study, we generated TcMICU1/TcMICU2 double knockout cell lines using CRISPR/Cas9 genome editing and found that these knockout cell lines were unable to uptake calcium at low extramitochondrial calcium concentrations. Further investigation revealed that Mg2+ negatively regulates the mitochondrial calcium uptake mediated by MCUC.
Editorial Material
Cell Biology
Roberto Docampo
Article
Neurosciences
Robert P. Brumer, Juliana C. Correa-Velloso, Samantha J. Thomas, Oleta A. Sandiford, Andrew P. Thomas, Paula J. Bartlett
Summary: Excessive consumption of carbohydrates, fat, and calories leads to non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance, which are major factors in the development of type II diabetes. Hormones and catecholamines regulate metabolic functions in the liver through G-protein coupled receptors (GPCRs) linked to phospholipase C (PLC) and increases in cytosolic calcium (Ca2+). However, a short-term high-fat diet (HFD) attenuates noradrenaline-stimulated Ca2+ signaling in hepatocytes and the intact liver.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Microbiology
Nuria W. Negrao, Logan P. Crowe, Brian S. Mantilla, Rodrigo P. Baptista, Sharon King-Keller, Guozhong Huang, Roberto Docampo
Summary: Trypanosoma brucei is the causative agent of African trypanosomiasis, and there is a need for new drugs due to limited treatment options and evidence of resistance. A phosphoinositide phospholipase C (TbPI-PLC-like) with an X and PDZ domain was discovered, similar to TbPI-PLC1. Recombinant TbPI-PLC-like does not hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) and does not modulate TbPI-PLC1 activity, but its knockdown affects the proliferation of trypanosomes.
Review
Microbiology
Roberto Docampo, Corrella S. Detweiler
Summary: Acidocalcisomes are organelles with acidity and high content of polyphosphate and calcium, and they have various functions and interactions with other organelles.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)