| 1. |
- Agostinho, Ana, et al.
(författare)
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High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation
- 2016
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Ingår i: EMBO Reports. - Stockholm : Wiley-VCH Verlagsgesellschaft. - 1469-221X .- 1469-3178. ; 17:6, s. 901-913
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Tidskriftsartikel (refereegranskat)abstract
- During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.
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| 2. |
- Andréasson, Claes, et al.
(författare)
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Mitochondria orchestrate proteostatic and metabolic stress responses
- 2019
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Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 20:10
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Tidskriftsartikel (refereegranskat)abstract
- The eukaryotic cell is morphologically and functionally organized as an interconnected network of organelles that responds to stress and aging. Organelles communicate via dedicated signal transduction pathways and the transfer of information in form of metabolites and energy levels. Recent data suggest that the communication between organellar proteostasis systems is a cornerstone of cellular stress responses in eukaryotic cells. Here, we discuss the integration of proteostasis and energy fluxes in the regulation of cellular stress and aging. We emphasize the molecular architecture of the regulatory transcriptional pathways that both sense and control metabolism and proteostasis. A special focus is placed on mechanistic insights gained from the model organism budding yeast in signaling from mitochondria to the nucleus and how this shapes cellular fitness.
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| 3. |
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| 4. |
- Berger, Birgit S., et al.
(författare)
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Parkinson's disease-associated receptor GPR37 is an ER chaperone for LRP6
- 2017
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Ingår i: EMBO Reports. - : Wiley-Blackwell Publishing Inc.. - 1469-221X .- 1469-3178. ; 18:5, s. 712-725
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Tidskriftsartikel (refereegranskat)abstract
- Wnt/beta-catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease-associated receptor GPR37 functions in the maturation of the N-terminal bulky beta-propellers of the Wnt co-receptor LRP6. GPR37 is required for Wnt/beta-catenin signaling and protects LRP6 from ER-associated degradation via CHIP (carboxyl terminus of Hsc70-interacting protein) and the ATPase VCP GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt-dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling.
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| 5. |
- Cruz Alsina, Fernando, et al.
(författare)
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Lrig1 is a cell-intrinsic modulator of hippocampal dendrite complexity and BDNF signaling
- 2016
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Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 17:4, s. 601-616
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Tidskriftsartikel (refereegranskat)abstract
- Even though many extracellular factors have been identified as promoters of general dendritic growth and branching, little is known about the cell-intrinsic modulators that allow neurons to sculpt distinctive patterns of dendrite arborization. Here, we identify Lrig1, a nervous system-enriched LRR protein, as a key physiological regulator of dendrite complexity of hippocampal pyramidal neurons. Lrig1-deficient mice display morphological changes in proximal dendrite arborization and defects in social interaction. Specifically, knockdown of Lrig1 enhances both primary dendrite formation and proximal dendritic branching of hippocampal neurons, two phenotypes that resemble the effect of BDNF on these neurons. In addition, we show that Lrig1 physically interacts with TrkB and attenuates BDNF signaling. Gain and loss of function assays indicate that Lrig1 restricts BDNF-induced dendrite morphology. Together, our findings reveal a novel and essential role of Lrig1 in regulating morphogenic events that shape the hippocampal circuits and establish that the assembly of TrkB with Lrig1 represents a key mechanism for understanding how specific neuronal populations expand the repertoire of responses to BDNF during brain development.
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| 6. |
- Dorafshan, Eshagh, et al.
(författare)
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Ash1 counteracts Polycomb repression independent of histone H3 lysine 36 methylation
- 2019
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Ingår i: EMBO Reports. - : WILEY. - 1469-221X .- 1469-3178. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb repression is critical for metazoan development. Equally important but less studied is the Trithorax system, which safeguards Polycomb target genes from the repression in cells where they have to remain active. It was proposed that the Trithorax system acts via methylation of histone H3 at lysine 4 and lysine 36 (H3K36), thereby inhibiting histone methyltransferase activity of the Polycomb complexes. Here we test this hypothesis by asking whether the Trithorax group protein Ash1 requires H3K36 methylation to counteract Polycomb repression. We show that Ash1 is the only Drosophila H3K36-specific methyltransferase necessary to prevent excessive Polycomb repression of homeotic genes. Unexpectedly, our experiments reveal no correlation between the extent of H3K36 methylation and the resistance to Polycomb repression. Furthermore, we find that complete substitution of the zygotic histone H3 with a variant in which lysine 36 is replaced by arginine does not cause excessive repression of homeotic genes. Our results suggest that the model, where the Trithorax group proteins methylate histone H3 to inhibit the histone methyltransferase activity of the Polycomb complexes, needs revision.
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| 7. |
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| 8. |
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| 9. |
- Evers, Kathinka, 1960-, et al.
(författare)
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Proactive epigenesis and ethics - Response
- 2017
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Ingår i: EMBO Reports. - : WILEY. - 1469-221X .- 1469-3178. ; 18:8, s. 1272-1272
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Hill, Sandra Malmgren, 1987, et al.
(författare)
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Restricted access: spatial sequestration of damaged proteins during stress and aging
- 2017
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Ingår i: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 18:3, s. 377-391
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Forskningsöversikt (refereegranskat)abstract
- The accumulation of damaged and aggregated proteins is a hallmark of aging and increased proteotoxic stress. To limit the toxicity of damaged and aggregated proteins and to ensure that the damage is not inherited by succeeding cell generations, a system of spatial quality control operates to sequester damaged/aggregated proteins into inclusions at specific protective sites. Such spatial sequestration and asymmetric segregation of damaged proteins have emerged as key processes required for cellular rejuvenation. In this review, we summarize findings on the nature of the different quality control sites identified in yeast, on genetic determinants required for spatial quality control, and on how aggregates are recognized depending on the stress generating them. We also briefly compare the yeast system to spatial quality control in other organisms. The data accumulated demonstrate that spatial quality control involves factors beyond the canonical quality control factors, such as chaperones and proteases, and opens up new venues in approaching how proteotoxicity might be mitigated, or delayed, upon aging.
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