The role of chaperone complex HSP90-SGT1-RAR1 as the associated machinery for hybrid inviability between Nicotiana gossei Domin and N. tabacum L.

Systematic affinity purification combined with mass spectrometry analysis of N- and C-tagged cytoplasmic Hsp70/Hsp110 chaperones was used to identify new roles of Hsp70/Hsp110 in the cell. This allowed the mapping of a chaperone–protein network consisting of 1,227 unique interactions between the 9 chaperones and 473 proteins and highlighted roles for Hsp70/Hsp110 in 14 broad biological processes. Using this information, we uncovered an essential role for Hsp110 in spindle assembly and, more specifically, in modulating the activity of the widely conserved kinesin-5 motor Cin8. The role of Hsp110 Sse1 as a nucleotide exchange factor for the Hsp70 chaperones Ssa1/Ssa2 was found to be required for maintaining the proper distribution of kinesin-5 motors within the spindle, which was subsequently required for bipolar spindle assembly in S phase. These data suggest a model whereby the Hsp70–Hsp110 chaperone complex antagonizes Cin8 plus-end motility and prevents premature spindle elongation in S phase.

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When acting as a reproductive barrier for sympatric speciation, hybrid sterility can only be primary

Biological Journal of the Linnean Society ◽

10.1093/biolinnean/blz135 ◽

2019 ◽

Vol 128 (4) ◽

pp. 779-788 ◽

Cited By ~ 2

Author(s):

Donald R Forsdyke

Keyword(s):

Hybrid Sterility ◽

Sympatric Speciation ◽

The Other ◽

Reproductive Barriers ◽

Evolutionary Time ◽

Hybrid Inviability ◽

Prezygotic Isolation ◽

Microscopic Scale ◽

A New Species

Abstract Animal gametes unite to form a zygote that develops into an adult with gonads that, in turn, produce gametes. Interruption of this germinal cycle by prezygotic or postzygotic reproductive barriers can result in two cycles, each with the potential to evolve into a new species. When the speciation process is complete, members of each species are fully reproductively isolated from those of the other. During speciation a primary barrier may be supported and eventually superceded by a later-appearing secondary barrier. For those holding certain cases of prezygotic isolation to be primary (e.g. elephant cannot copulate with mouse), the onus is to show that they had not been preceded over evolutionary time by periods of postzygotic hybrid inviability (genically determined) or sterility (genically or chromosomally determined). Likewise, the onus is upon those holding cases of hybrid inviability to be primary (e.g. Dobzhansky–Muller epistatic incompatibilities) to show that they had not been preceded by periods, however brief, of hybrid sterility. The latter, when acting as a sympatric barrier causing reproductive isolation, can only be primary. In many cases, hybrid sterility may result from incompatibilities between parental chromosomes that attempt to pair during meiosis in the gonad of their offspring (Winge-Crowther-Bateson incompatibilities). While such incompatibilities have long been observed on a microscopic scale, there is growing evidence for a role of dispersed finer DNA sequence differences (i.e. in base k-mers).

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Individualized management of genetic diversity in Niemann-Pick C1 through modulation of the Hsp70 chaperone system

Human Molecular Genetics ◽

10.1093/hmg/ddz215 ◽

2019 ◽

Vol 29 (1) ◽

pp. 1-19 ◽

Cited By ~ 3

Author(s):

Chao Wang ◽

Samantha M Scott ◽

Shuhong Sun ◽

Pei Zhao ◽

Darren M Hutt ◽

...

Keyword(s):

Genetic Diversity ◽

Transmembrane Protein ◽

Genetic Disorder ◽

Cholesterol Homeostasis ◽

Spatial Covariance ◽

Spatial Profiling ◽

Hsp70 Chaperone ◽

Niemann Pick ◽

Chaperone Complex

Abstract Genetic diversity provides a rich repository for understanding the role of proteostasis in the management of the protein fold in human biology. Failure in proteostasis can trigger multiple disease states, affecting both human health and lifespan. Niemann-Pick C1 (NPC1) disease is a rare genetic disorder triggered by mutations in NPC1, a multi-spanning transmembrane protein that is trafficked through the exocytic pathway to late endosomes (LE) and lysosomes (Ly) (LE/Ly) to globally manage cholesterol homeostasis. Defects triggered by >300 NPC1 variants found in the human population inhibit export of NPC1 protein from the endoplasmic reticulum (ER) and/or function in downstream LE/Ly, leading to cholesterol accumulation and onset of neurodegeneration in childhood. We now show that the allosteric inhibitor JG98, that targets the cytosolic Hsp70 chaperone/co-chaperone complex, can significantly improve the trafficking and post-ER protein level of diverse NPC1 variants. Using a new approach to model genetic diversity in human disease, referred to as variation spatial profiling, we show quantitatively how JG98 alters the Hsp70 chaperone/co-chaperone system to adjust the spatial covariance (SCV) tolerance and set-points on an amino acid residue-by-residue basis in NPC1 to differentially regulate variant trafficking, stability, and cholesterol homeostasis, results consistent with the role of BCL2-associated athanogene family co-chaperones in managing the folding status of NPC1 variants. We propose that targeting the cytosolic Hsp70 system by allosteric regulation of its chaperone/co-chaperone based client relationships can be used to adjust the SCV tolerance of proteostasis buffering capacity to provide an approach to mitigate systemic and neurological disease in the NPC1 population.

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Histone H3.3 Hira chaperone complex contributes to zygote formation in mice and humans

10.1101/2020.06.18.159954 ◽

2020 ◽

Author(s):

Rowena Smith ◽

Sue Pickering ◽

Anna Kopakaki ◽

K Joo Thong ◽

Richard A Anderson ◽

...

Keyword(s):

Sperm Chromatin ◽

Proof Of Concept ◽

Loss Of Function ◽

Male Pronucleus ◽

Histone H3.3 ◽

Infertile Couples ◽

Chaperone Complex ◽

Chromatin Reprogramming ◽

Histone Exchange

AbstractElucidating the underlining mechanisms underpinning successful fertilisation is imperative in optimising IVF treatments, and may lead to a specific diagnosis and therefore potential treatment for some infertile couples. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. This step is critical for the formation of the male pronucleus, without which the zygote contains only 1 pronucleus (1PN), in contrast to normally fertilised zygotes with two-pronuclei (2PN). 1PN zygotes are a frequently observed phenomenon in IVF treatments, therefore aberrant mechanism of action controlling paternal chromatin repackaging may be an important cause of abnormal fertilisation. Hira is the main H3.3 chaperone that governs this protamine-to-histone exchange. In this study, we investigated the maternal functions of two other molecules of the Hira complex, Cabin1 and Ubn1 in the mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed abnormal 1PN zygote phenotypes, similar to the phenotype of Hira mutants. We then studied human 1PN zygotes, and found that the Hira complex was absent in 1PN zygotes which were lacking the male pronucleus. This result confirms that the role of the Hira complex in male pronucleus formation has coherence from mice to humans. Furthermore, rescue experiments showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of Hira in the mouse oocytes. In summary, we have provided evidence of the role of Hira complex in regulating male pronucleus formation in both mice and humans, that both Cabin1 and Ubn1 components of the Hira complex are equally essential for male pronucleus formation, and that this can be rescued. We present a proof-of-concept experiment that could potentially lead to a personalised IVF therapy for oocyte defects.

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Patterns of hybrid seed inviability in perennials of the Mimulus guttatus sp. complex reveal a potential role of parental conflict in reproductive isolation

10.1101/458315 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jenn M. Coughlan ◽

Maya Wilson Brown ◽

John H. Willis

Keyword(s):

Resource Allocation ◽

Reproductive Isolation ◽

Potential Role ◽

Rapid Evolution ◽

Hybrid Seed ◽

Parental Conflict ◽

Reproductive Barriers ◽

Hybrid Inviability ◽

Parent Of Origin

SummaryGenomic conflicts may play a central role in the evolution of reproductive barriers. Theory predicts that early-onset hybrid inviability may stem from conflict between parents for resource allocation to offspring. Here we describe M. decorus; a group of cryptic species within the M. guttatus species complex that are largely reproductively isolated by hybrid seed inviability (HSI). HSI between M. guttatus and M. decorus is common and strong, but populations of M. decorus vary in the magnitude and directionality of HSI with M. guttatus. Patterns of HSI between M. guttatus and M. decorus, as well as within M. decorus conform to the predictions of parental conflict: (1) reciprocal F1s exhibit size differences and parent-of-origin specific endosperm defects, (2) the extent of asymmetry between reciprocal F1 seed size is correlated with asymmetry in HSI, and (3) inferred differences in the extent of conflict predict the extent of HSI between populations. We also find that HSI is rapidly evolving, as populations that exhibit the most HSI are each others’ closest relative. Lastly, while all populations are largely outcrossing, we find that the differences in the inferred strength of conflict scale positively with π, suggesting that demographic or life history factors other than mating system may also influence the rate of parental conflict driven evolution. Overall, these patterns suggest the rapid evolution of parent-of-origin specific resource allocation alleles coincident with HSI within and between M. guttatus and M. decorus. Parental conflict may therefore be an important evolutionary driver of reproductive isolation.

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The Heat Shock Protein 70 Cochaperone YDJ1 Is Required for Efficient Membrane-Specific Flock House Virus RNA Replication Complex Assembly and Function in Saccharomyces cerevisiae

Journal of Virology ◽

10.1128/jvi.02017-07 ◽

2007 ◽

Vol 82 (4) ◽

pp. 2004-2012 ◽

Cited By ~ 27

Author(s):

Spencer A. Weeks ◽

David J. Miller

Keyword(s):

Rna Replication ◽

Viral Rna ◽

Flock House Virus ◽

Complex Activity ◽

Complex Assembly ◽

Replication Complex ◽

Hsp90 Chaperone ◽

Chaperone Complex ◽

And Function

ABSTRACT The assembly of RNA replication complexes on intracellular membranes is an essential step in the life cycle of positive-sense RNA viruses. We have previously shown that Hsp90 chaperone complex activity is essential for efficient Flock House virus (FHV) RNA replication in Drosophila melanogaster S2 cells. To further explore the role of cellular chaperones in viral RNA replication, we used both pharmacologic and genetic approaches to examine the role of the Hsp90 and Hsp70 chaperone systems in FHV RNA replication complex assembly and function in Saccharomyces cerevisiae. In contrast to results with insect cells, yeast deficient in Hsp90 chaperone complex activity showed no significant decrease in FHV RNA replication. However, yeast with a deletion of the Hsp70 cochaperone YDJ1 showed a dramatic reduction in FHV RNA replication that was due in part to reduced viral RNA polymerase accumulation. Furthermore, the absence of YDJ1 did not reduce FHV RNA replication when the viral RNA polymerase and replication complexes were retargeted from the mitochondria to the endoplasmic reticulum. These results identify YDJ1 as an essential membrane-specific host factor for FHV RNA replication complex assembly and function in S. cerevisiae and are consistent with known differences in the role of distinct chaperone complexes in organelle-specific protein targeting between yeast and higher eukaryotes.

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The PopN gate-keeper complex acts on the ATPase PscN to regulate the T3SS secretion switch from early to middle substrates in Pseudomonas aeruginosa

10.1101/2020.07.28.224923 ◽

2020 ◽

Author(s):

Tuan-Dung Ngo ◽

Caroline Perdu ◽

Bakhos Jneid ◽

Michel Ragno ◽

Julia Novion Ducassou ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Type Iii Secretion ◽

Secreted Proteins ◽

List Type ◽

Protein Protein Interaction ◽

Microscale Thermophoresis ◽

Wide Range ◽

Chaperone Complex ◽

Bacterial Cytoplasm

AbstractPseudomonas aeruginosa is an opportunistic bacterium of which the main virulence factor is the Type III Secretion System. The ATPase of this machinery, PscN (SctN), is thought to be localized at the base of the secretion apparatus and to participate in the recognition, chaperone dissociation and unfolding of exported T3SS proteins. In this work, a protein-protein interaction ELISA revealed the interaction of PscN with a wide range of exported T3SS proteins including the needle, translocator, gate-keeper and effector. These interactions were further confirmed by Microscale Thermophoresis that also indicated a preferential interaction of PscN with secreted proteins or protein-chaperone complex rather than with chaperones alone, in line with the release of the chaperones in the bacterial cytoplasm after the dissociation from their exported proteins. Moreover, we suggest a new role of the gate-keeper complex and the ATPase in the regulation of early substrates recognition by the T3SS. This finding sheds a new light on the mechanism of secretion switching from early to middle substrates in P. aeruginosa.HighlightsT3SS substrates are secreted sequentially but information on the switches are missingInteraction of the T3SS ATPase with secreted proteins were investigated by different approachesMicroscale Thermophoresis revealed a lower affinity for chaperones alone compared to complexesThe Gate-keeper complex binds to the ATPase and increases its affinity for the needle complexA new role of the Gate-keeper complex is proposed, directly acting on the T3SS ATPase

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ROLE OF R2TP COMPLEX IN LYMPHOMA AND ITS THERAPEUTIC POTENTIAL

International Journal of Advanced Research ◽

10.21474/ijar01/12010 ◽

2020 ◽

Vol 8 (11) ◽

pp. 300-303

Author(s):

Moien Lone ◽

◽

Qulsum Akhter ◽

Mithilesh Kumar ◽

Umar Maqbool ◽

...

Keyword(s):

Tumor Suppressor ◽

Rna Polymerase Ii ◽

Therapeutic Potential ◽

Phosphatidylinositol 3 Kinase ◽

Cellular Processes ◽

Proliferation Activity ◽

Multimeric Protein ◽

Chaperone Complex ◽

Hsp 90

The R2TP complex which comprises of RUVBL1, RUVBL2, PIH1D1 and RPAP3 in humans is known to be a specialized Co-chaperone of Hsp-90 protein. This multimeric-protein complex is involved in the assembly and maturation of several multi-subunit complexes including RNA polymerase II, small nucleolar ribonucleoproteins, and complexes containing phosphatidylinositol-3-kinase-like kinases. Since their discovery as a co-chaperone of Hsp90, the R2TP complex is involved in multitude of cellular processes including, chromatin remodelling, transcription regulation, ribonucleoprotein complex biogenesis, mitotic assembly, telomerase complex assembly, and apoptosis. Lymphoma arises from the abnormal proliferation of B-cells and the R2TP complex have been reported to play an important role in the activation of p53 and RB. Therefore, the inactivation in any of the tumor suppressor pathways can drive cells to malignancy.However, there are multiple factors which may contribute towards malignancy but the folding defects in these tumor suppressor pathways could be one of the reasons. R2TP is tightly linked with oncogenesis and its inhibition can decrease the proliferation activity of cancer cells. So, the multisubunit chaperone complex as well as its components could be promising candidates for cancer chemotherapy.

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Survival protection mechanisms and genetic variability induction after stress: two sides of the same Hsp70 coin

10.1101/423210 ◽

2018 ◽

Author(s):

Ugo Cappucci ◽

Fabrizia Noro ◽

Assunta Maria Casale ◽

Laura Fanti ◽

Maria Berloco ◽

...

Keyword(s):

Heat Shock ◽

Genetic Variability ◽

Environmental Changes ◽

Decisive Role ◽

Transcriptional Level ◽

Heat Shock Stress ◽

Chaperone Complex ◽

Chaperone Hsp70 ◽

Shock Stress

AbstractPrevious studies have shown that heat shock stress may increase transcription levels and, in some cases, also the transposition of certain transposable elements (TEs) in Drosophila and other organisms. Other studies have also demonstrated that heat shock chaperones as Hsp90 and Hop are involved in repressing transposon’s activity in Drosophila melanogaster by their involvement in crucial steps of the biogenesis of Piwi-interacting RNAs (piRNAs), the largest class of germline-enriched small non-coding RNA implicated in the epigenetic silencing of TEs. However, a satisfying picture of how many chaperones and their respective functional roles could be involved in repressing transposons in germ cell is still unknown. Here we show that in Drosophila heat shock activates transposon′s expression at post-transcriptional level by disrupting a repressive chaperone complex by a decisive role of the stress-inducible chaperone Hsp70. We found that stress-induced transposons activation is triggered by an interaction of Hsp70 with the Hsc70-Hsp90 complex and other factors all involved in piRNA biogenesis in both ovaries and testes. Such interaction induces a displacement of all such factors to the lysosomes resulting in a functional collapse of piRNA biogenesis. In support of a significant role of Hsp70 in transposon activation after stress, we found that the expression under normal conditions of Hsp70 in transgenic flies increases the amount of transposon transcripts and displaces the components of chaperon machinery outside the nuage as observed after heat shock. So that, our results demonstrate that heat shock stress is capable to increase the expression of transposons at post-transcriptional level by affecting piRNA biogenesis through the action of the inducible chaperone Hsp70. We think that such mechanism proposes relevant evolutionary implications. In presence of drastic environmental changes, Hsp70 plays a key dual role in increasing both the survival probability of individuals and the genetic variability in their germ cells. This in turn should be translated into an increase of genetic variability inside the populations thus potentiating their evolutionary plasticity and evolvability.

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The R2TP chaperone complex: its involvement in snoRNP assembly and tumorigenesis

BioMolecular Concepts ◽

10.1515/bmc-2014-0028 ◽

2014 ◽

Vol 5 (6) ◽

pp. 513-520 ◽

Cited By ~ 12

Author(s):

Yoshito Kakihara ◽

Makio Saeki

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Proliferation ◽

Rna Polymerase ◽

Cellular Processes ◽

Snornp Biogenesis ◽

Chaperone Complex

AbstractR2TP was originally identified in yeast Saccharomyces cerevisiae as Hsp90 interacting complex, and is composed of four different proteins: Rvb1, Rvb2, Tah1, and Pih1. This complex is well-conserved in eukaryotes, and is involved in many cellular processes such as snoRNP biogenesis, RNA polymerase assembly, PIKK signaling, and apoptosis. An increasing number of research related to R2TP suggests a linkage of its function with tumorigenesis. In this review, we provide an overview of several recent studies on R2TP that are related to cell proliferation and carcinogenesis, and propose a possible role of R2TP in tumorigenesis through regulating snoRNA/snoRNP biogenesis.

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