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Frontiers in Cellular and Infection... 2020Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as... (Review)
Review
Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as () and avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking. In this review, the mechanisms by which the respective pathogen containing vacuoles (PCVs) intersect with lysosomal trafficking pathways and maintain their distinctness are discussed. Despite such active inhibition of lysosomal targeting, emerging literature shows that different pathogens or pathogen derived products exhibit a global influence on the host lysosomal system. Pathogen mediated lysosomal enrichment promotes the trafficking of a sub-set of pathogens to lysosomes, indicating heterogeneity in the host-pathogen encounter. This review integrates recent advancements on the global lysosomal alterations upon infections and the host protective role of the lysosomes against these pathogens. The review also briefly discusses the heterogeneity in the lysosomal targeting of these pathogens and the possible mechanisms and consequences.
Topics: Host-Pathogen Interactions; Lysosomes; Mycobacterium tuberculosis; Vacuoles
PubMed: 33330138
DOI: 10.3389/fcimb.2020.595502 -
Rheumatology (Oxford, England) Dec 2023
Topics: Humans; Vacuoles; Mutation
PubMed: 37522863
DOI: 10.1093/rheumatology/kead392 -
The New Phytologist Apr 2020Vacuolar processing enzyme (VPE) is a cysteine-type endopeptidase that has a substrate-specificity for asparagine or aspartic acid residues and cleaves peptide bonds at... (Review)
Review
Vacuolar processing enzyme (VPE) is a cysteine-type endopeptidase that has a substrate-specificity for asparagine or aspartic acid residues and cleaves peptide bonds at their carboxyl-terminal side. Various vacuolar proteins are synthesized as larger proprotein precursors, and VPE is an important initiator of maturation and activation of these proteins. It mediates programmed cell death (PCD) by provoking vacuolar rupture and initiating the proteolytic cascade leading to PCD. Vacuolar processing enzyme also possesses a peptide ligation activity, which is responsible for producing cyclic peptides in several plant species. These unique functions of VPE support developmental and environmental responses in plants. The number of VPE homologues is higher in angiosperm species, indicating that there has been differentiation and specialization of VPE function over the course of evolution. Angiosperm VPEs are separated into two major types: the γ-type VPEs, which are expressed mainly in vegetative organs, and the β-type VPEs, whose expression occurs mainly in storage organs; in eudicots, the δ-type VPEs are further separated within γ-type VPEs. This review also considers the importance of processing and peptide ligation by VPE in vacuolar protein maturation.
Topics: Animals; Cysteine Endopeptidases; Life Cycle Stages; Plant Proteins; Plants; Vacuoles
PubMed: 31679161
DOI: 10.1111/nph.16306 -
The Journal of Cell Biology Oct 2019Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even with an elaborate network of molecular chaperones and protein folding... (Review)
Review
Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even with an elaborate network of molecular chaperones and protein folding facilitators, misfolding can occur quite frequently. To maintain protein homeostasis, eukaryotes have evolved a series of protein quality-control checkpoints. When secretory pathway quality-control pathways fail, stress response pathways, such as the unfolded protein response (UPR), are induced. In addition, the ER, which is the initial hub of protein biogenesis in the secretory pathway, triages misfolded proteins by delivering substrates to the proteasome or to the lysosome/vacuole through ER-associated degradation (ERAD) or ER-phagy. Some misfolded proteins escape the ER and are instead selected for Golgi quality control. These substrates are targeted for degradation after retrieval to the ER or delivery to the lysosome/vacuole. Here, we discuss how these guardian pathways function, how their activities intersect upon induction of the UPR, and how decisions are made to dispose of misfolded proteins in the secretory pathway.
Topics: Animals; Endoplasmic Reticulum; Humans; Lysosomes; Proteins; Secretory Pathway; Vacuoles
PubMed: 31537714
DOI: 10.1083/jcb.201906047 -
Journal of Experimental Botany Mar 2022Seed storage proteins (SSPs) are of great importance in plant science and agriculture, particularly in cereal crops, due to their nutritional value and their impact on... (Review)
Review
Seed storage proteins (SSPs) are of great importance in plant science and agriculture, particularly in cereal crops, due to their nutritional value and their impact on food properties. During seed maturation, massive amounts of SSPs are synthesized and deposited either within protein bodies derived from the endoplasmic reticulum, or into specialized protein storage vacuoles (PSVs). The processing and trafficking of SSPs vary among plant species, tissues, and even developmental stages, as well as being influenced by SSP composition. The different trafficking routes, which affect the amount of SSPs that seeds accumulate and their composition and modifications, rely on a highly dynamic and functionally specialized endomembrane system. Although the general steps in SSP trafficking have been studied in various plants, including cereals, the detailed underlying molecular and regulatory mechanisms are still elusive. In this review, we discuss the main endomembrane routes involved in SSP trafficking to the PSV in Arabidopsis and other eudicots, and compare and contrast the SSP trafficking pathways in major cereal crops, particularly in rice and maize. In addition, we explore the challenges and strategies for analyzing the endomembrane system in cereal crops.
Topics: Arabidopsis; Arabidopsis Proteins; Edible Grain; Protein Transport; Seed Storage Proteins; Seeds; Vacuoles
PubMed: 34849750
DOI: 10.1093/jxb/erab519 -
Proceedings of the National Academy of... May 2023Vac8, a yeast vacuolar protein with armadillo repeats, mediates various cellular processes by changing its binding partners; however, the mechanism by which Vac8...
Vac8, a yeast vacuolar protein with armadillo repeats, mediates various cellular processes by changing its binding partners; however, the mechanism by which Vac8 differentially regulates these processes remains poorly understood. Vac8 interacts with Nvj1 to form the nuclear-vacuole junction (NVJ) and with Atg13 to mediate cytoplasm-to-vacuole targeting (Cvt), a selective autophagy-like pathway that delivers cytoplasmic aminopeptidase I directly to the vacuole. In addition, Vac8 associates with Myo2, a yeast class V myosin, through its interaction with Vac17 for vacuolar inheritance from the mother cell to the emerging daughter cell during cell divisions. Here, we determined the X-ray crystal structure of the Vac8-Vac17 complex and found that its interaction interfaces are bipartite, unlike those of the Vac8-Nvj1 and Vac8-Atg13 complexes. When the key amino acids present in the interface between Vac8 and Vac17 were mutated, vacuole inheritance was severely impaired in vivo. Furthermore, binding of Vac17 to Vac8 prevented dimerization of Vac8, which is required for its interactions with Nvj1 and Atg13, by clamping the H1 helix to the ARM1 domain of Vac8 and thereby preventing exposure of the binding interface for Vac8 dimerization. Consistently, the binding affinity of Vac17-bound Vac8 for Nvj1 or Atg13 was markedly lower than that of free Vac8. Likewise, free Vac17 had no affinity for the Vac8-Nvj1 and Vac8-Atg13 complexes. These results provide insights into how vacuole inheritance and other Vac8-mediated processes, such as NVJ formation and Cvt, occur independently of one another.
Topics: Saccharomyces cerevisiae; Vesicular Transport Proteins; Saccharomyces cerevisiae Proteins; Vacuoles; Cytoplasm; Protein Transport; Autophagy; Autophagy-Related Proteins; Adaptor Proteins, Signal Transducing; Receptors, Cell Surface
PubMed: 37094131
DOI: 10.1073/pnas.2211501120 -
PLoS Pathogens Jul 2023L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330...
L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector localizes to endosomes and remodels host actin cytoskeleton in a phosphatidylinositol 3-phosphate (PI(3)P) dependent manner when ectopically expressed. We show that MavH recruits host actin capping protein (CP) and actin to the endosome via its CP-interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates actin assembly on PI(3)P-containing liposomes causing their tubulation. In addition, the recruitment of CP by MavH negatively regulates F-actin density at the membrane. We further show that, in L. pneumophila-infected cells, MavH appears around the LCV at the very early stage of infection and facilitates bacterium entry into the host. Together, our results reveal a novel mechanism of membrane tubulation induced by membrane-dependent actin polymerization catalyzed by MavH that contributes to the early stage of L. pneumophila infection by regulating host actin dynamics.
Topics: Legionella pneumophila; Actins; Polymerization; Phosphatidylinositol Phosphates; Vacuoles; Bacterial Proteins
PubMed: 37463171
DOI: 10.1371/journal.ppat.1011512 -
The New Phytologist Feb 2020Active removal of Na from the cytosol into the vacuole plays a critical role in salinity tissue tolerance, but another, often neglected component of this trait is Na... (Review)
Review
Active removal of Na from the cytosol into the vacuole plays a critical role in salinity tissue tolerance, but another, often neglected component of this trait is Na retention in vacuoles. This retention is based on an efficient control of Na -permeable slow- and fast-vacuolar channels that mediate the back-leak of Na into cytosol and, if not regulated tightly, could result in a futile cycle. This Tansley insight summarizes our current knowledge of regulation of tonoplast Na -permeable channels and discusses the energy cost of vacuolar Na sequestration, under different scenarios. We also report on a phylogenetic and bioinformatic analysis of the plant two-pore channel family and the difference in its structure and regulation between halophytes and glycophytes, in the context of salinity tolerance.
Topics: Energy Metabolism; Plant Proteins; Proton Pumps; Salt-Tolerant Plants; Sodium; Vacuoles
PubMed: 30802968
DOI: 10.1111/nph.15758 -
The Lancet. Haematology Feb 2024The presence of vacuoles in myeloid and erythroid progenitor cells in bone marrow aspirates is a key feature of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic... (Review)
Review
The presence of vacuoles in myeloid and erythroid progenitor cells in bone marrow aspirates is a key feature of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The mere observation of vacuolated progenitor cells is not specific to VEXAS syndrome; in this Viewpoint, we point out the causes to be considered in this situation. Vacuoles, in particular, can be observed in individuals with wild-type UBA1 and with persistent inflammatory features or myelodysplastic syndromes. However, several clues support the diagnosis of VEXAS syndrome in the presence of vacuolated bone marrow progenitors: a high number of vacuolated progenitors and of vacuoles per cell, the predominance of vacuoles in early rather than late progenitors, and the vacuolisation of both myeloid and erythroid progenitors with predominance of myeloid ones. Some criteria derived from these observations have been proposed with great diagnostic performances. However, the absence or a low proportion of vacuolated cells should not prevent UBA1 gene sequencing.
Topics: Humans; Bone Marrow; Vacuoles; Myelodysplastic Syndromes; Mutation; Skin Diseases, Genetic
PubMed: 38302223
DOI: 10.1016/S2352-3026(23)00375-7 -
Journal of Experimental Botany Mar 2022Nearly 10% of all plant proteins belong to the zinc (Zn) proteome. They require Zn either for catalysis or as a structural element. Most of the protein-bound Zn in...
Nearly 10% of all plant proteins belong to the zinc (Zn) proteome. They require Zn either for catalysis or as a structural element. Most of the protein-bound Zn in eukaryotic cells is found in the cytosol. The fundamental differences between transition metal cations in the stability of their complexes with organic ligands, as described by the Irving-Williams series, necessitate buffering of cytosolic Zn (the 'free Zn' pool) in the picomolar range (i.e. ~6 orders of magnitude lower than the total cellular concentration). Various metabolites and peptides, including nicotianamine, glutathione, and phytochelatins, serve as Zn buffers. They are hypothesized to supply Zn to enzymes, transporters, or the recently identified sensor proteins. Zn2+ acquisition is mediated by ZRT/IRT-like proteins. Metal tolerance proteins transport Zn2+ into vacuoles and the endoplasmic reticulum, the major Zn storage sites. Heavy metal ATPase-dependent efflux of Zn2+ is another mechanism to control cytosolic Zn. Spatially controlled Zn2+ influx or release from intracellular stores would result in dynamic modulation of cellular Zn pools, which may directly influence protein-protein interactions or the activities of enzymes involved in signaling cascades. Possible regulatory roles of such changes, as recently elucidated in mammalian cells, are discussed.
Topics: Animals; Mammals; Membrane Transport Proteins; Metals; Vacuoles; Zinc
PubMed: 34727160
DOI: 10.1093/jxb/erab481