A novel mechanosensitive channel controls osmoregulation, differentiation, and infectivity in Trypanosoma cruzi
Copyright policy )A novel mechanosensitive channel controls osmoregulation, differentiation, and infectivity in Trypanosoma cruzi
The causative agent of Chagas disease undergoes drastic morphological and biochemical modifications as it passes between hosts and transitions from extracellular to intracellular stages. The osmotic and mechanical aspects of these cellular transformations are not understood. Here we identify and characterize a novel mechanosensitive channel in T rypanosoma cruzi (TcMscS) belonging to the superfamily of small-conductance mechanosensitive channels (MscS). TcMscS is activated by membrane tension and forms a large pore permeable to anions, cations, and small osmolytes. The channel changes its location from the contractile vacuole complex in epimastigotes to the plasma membrane as the parasites develop into intracellular amastigotes. TcMscS knockout parasites show significant fitness defects, including increased cell volume, calcium dysregulation, impaired differentiation, and a dramatic decrease in infectivity. Our work provides mechanistic insights into components supporting pathogen adaptation inside the host, thus opening the exploration of mechanosensation as a prerequisite for protozoan infectivity.
- National Scientific and Technical Research Council Argentina
- University System of Ohio United States
- Facultad de Ciencias Agrarias y Forestales Argentina
- University of Maryland United States
- CALIFORNIA STATE UNIVERSITY FULLERTON
Protein Conformation, Epidemiology, Physiology, Epidemiology and Treatment of Chagas Disease, Protozoan Proteins, Extracellular, Antibodies, Protozoan, Mechanosensitive channels, Mechanotransduction, Cellular, Biochemistry, Ion Channels, Osmoregulation, https://purl.org/becyt/ford/1.6, Parasite hosting, mechanosensation, Biology (General), Cloning, Molecular, Microbiology and Infectious Disease, Q, R, Life Sciences, Cell Differentiation, Virus, World Wide Web, CRISPR-CAS9, Medicine, CRISPR-Cas9, Ion channel, Receptor, Cell biology, QH301-705.5, Osmolyte, Science, Trypanosoma cruzi, Immunology, Osmotic Pressure, Biochemistry, Genetics and Molecular Biology, Health Sciences, Humans, INFECTIVITY, https://purl.org/becyt/ford/1, Molecular Biology, Biology, Lysosomal Calcium Signaling in Physiology and Pathology, calcium, FOS: Clinical medicine, Computational Biology, TRYPANOSOMA CRUZI, electrophysiology, Computer science, Intracellular, Electrophysiological Phenomena, Molecular Mechanisms of Ion Channels Regulation, HEK293 Cells, Gene Expression Regulation, Infectivity, MECHANOSENSATION, FOS: Biological sciences, Mutation, Calcium, CRISPR-Cas Systems, osmoregulation, Mechanosensation
Protein Conformation, Epidemiology, Physiology, Epidemiology and Treatment of Chagas Disease, Protozoan Proteins, Extracellular, Antibodies, Protozoan, Mechanosensitive channels, Mechanotransduction, Cellular, Biochemistry, Ion Channels, Osmoregulation, https://purl.org/becyt/ford/1.6, Parasite hosting, mechanosensation, Biology (General), Cloning, Molecular, Microbiology and Infectious Disease, Q, R, Life Sciences, Cell Differentiation, Virus, World Wide Web, CRISPR-CAS9, Medicine, CRISPR-Cas9, Ion channel, Receptor, Cell biology, QH301-705.5, Osmolyte, Science, Trypanosoma cruzi, Immunology, Osmotic Pressure, Biochemistry, Genetics and Molecular Biology, Health Sciences, Humans, INFECTIVITY, https://purl.org/becyt/ford/1, Molecular Biology, Biology, Lysosomal Calcium Signaling in Physiology and Pathology, calcium, FOS: Clinical medicine, Computational Biology, TRYPANOSOMA CRUZI, electrophysiology, Computer science, Intracellular, Electrophysiological Phenomena, Molecular Mechanisms of Ion Channels Regulation, HEK293 Cells, Gene Expression Regulation, Infectivity, MECHANOSENSATION, FOS: Biological sciences, Mutation, Calcium, CRISPR-Cas Systems, osmoregulation, Mechanosensation
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