LIVIVO - Search results -

Search results

Result 1 - 10 of total 66

Search options

Article ; Online: Systematically defining selective autophagy receptor-specific cargo using autophagosome content profiling.

Zellner, Susanne / Schifferer, Martina / Behrends, Christian

2021 Volume 81, Issue 6, Page(s) 1337–1354.e8

Abstract: Autophagy deficiency in fed conditions leads to the formation of protein inclusions highlighting the contribution of this lysosomal delivery route to cellular proteostasis. Selective autophagy pathways exist that clear accumulated and aggregated ... ...

Abstract	Autophagy deficiency in fed conditions leads to the formation of protein inclusions highlighting the contribution of this lysosomal delivery route to cellular proteostasis. Selective autophagy pathways exist that clear accumulated and aggregated ubiquitinated proteins. Receptors for this type of autophagy (aggrephagy) include p62, NBR1, TOLLIP, and OPTN, which possess LC3-interacting regions and ubiquitin-binding domains (UBDs), thus working as a bridge between LC3/GABARAP proteins and ubiquitinated substrates. However, the identity of aggrephagy substrates and the redundancy of aggrephagy and related UBD-containing receptors remains elusive. Here, we combined proximity labeling and organelle enrichment with quantitative proteomics to systematically map the autophagic degradome targeted by UBD-containing receptors under basal and proteostasis-challenging conditions in human cell lines. We identified various autophagy substrates, some of which were differentially engulfed by autophagosomal and endosomal membranes via p62 and TOLLIP, respectively. Overall, this resource will allow dissection of the proteostasis contribution of autophagy to numerous individual proteins.
MeSH term(s)	Autophagosomes/genetics ; Autophagosomes/metabolism ; Autophagy ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Protein Interaction Maps ; Proteolysis ; Proteomics ; Proteostasis ; Ubiquitination
Chemical Substances	Autophagy-Related Proteins
Language	English
Publishing date	2021-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2021.01.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5055: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Niwaki Instead of Random Forests: Targeted Serial Sectioning Scanning Electron Microscopy With Reimaging Capabilities for Exploring Central Nervous System Cell Biology and Pathology.

Schifferer, Martina / Snaidero, Nicolas / Djannatian, Minou / Kerschensteiner, Martin / Misgeld, Thomas

Frontiers in neuroanatomy

2021 Volume 15, Page(s) 732506

Abstract: Ultrastructural analysis of discrete neurobiological structures by volume scanning electron microscopy (SEM) often constitutes a "needle-in-the-haystack" problem and therefore relies on sophisticated search strategies. The appropriate SEM approach for a ... ...

Abstract	Ultrastructural analysis of discrete neurobiological structures by volume scanning electron microscopy (SEM) often constitutes a "needle-in-the-haystack" problem and therefore relies on sophisticated search strategies. The appropriate SEM approach for a given relocation task not only depends on the desired final image quality but also on the complexity and required accuracy of the screening process. Block-face SEM techniques like Focused Ion Beam or serial block-face SEM are "one-shot" imaging runs by nature and, thus, require precise relocation prior to acquisition. In contrast, "multi-shot" approaches conserve the sectioned tissue through the collection of serial sections onto solid support and allow reimaging. These tissue libraries generated by Array Tomography or Automated Tape Collecting Ultramicrotomy can be screened at low resolution to target high resolution SEM. This is particularly useful if a structure of interest is rare or has been predetermined by correlated light microscopy, which can assign molecular, dynamic and functional information to an ultrastructure. As such approaches require bridging mm to nm scales, they rely on tissue trimming at different stages of sample processing. Relocation is facilitated by endogenous or exogenous landmarks that are visible by several imaging modalities, combined with appropriate registration strategies that allow overlaying images of various sources. Here, we discuss the opportunities of using multi-shot serial sectioning SEM approaches, as well as suitable trimming and registration techniques, to slim down the high-resolution imaging volume to the actual structure of interest and hence facilitate ambitious targeted volume SEM projects.
Language	English
Publishing date	2021-10-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452969-2
ISSN	1662-5129
ISSN	1662-5129
DOI	10.3389/fnana.2021.732506
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A new form of axonal pathology in a spinal model of neuromyelitis optica.

Herwerth, Marina / Kenet, Selin / Schifferer, Martina / Winkler, Anne / Weber, Melanie / Snaidero, Nicolas / Wang, Mengzhe / Lohrberg, Melanie / Bennett, Jeffrey L / Stadelmann, Christine / Hemmer, Bernhard / Misgeld, Thomas

Brain : a journal of neurology

2024 Volume 145, Issue 5, Page(s) 1726–1742

Abstract: Neuromyelitis optica is a chronic neuroinflammatory disease, which primarily targets astrocytes and often results in severe axon injury of unknown mechanism. Neuromyelitis optica patients harbour autoantibodies against the astrocytic water channel ... ...

Abstract	Neuromyelitis optica is a chronic neuroinflammatory disease, which primarily targets astrocytes and often results in severe axon injury of unknown mechanism. Neuromyelitis optica patients harbour autoantibodies against the astrocytic water channel protein, aquaporin-4 (AQP4-IgG), which induce complement-mediated astrocyte lysis and subsequent axon damage. Using spinal in vivo imaging in a mouse model of such astrocytopathic lesions, we explored the mechanism underlying neuromyelitis optica-related axon injury. Many axons showed a swift and morphologically distinct 'pearls-on-string' transformation also readily detectable in human neuromyelitis optica lesions, which especially affected small calibre axons independently of myelination. Functional imaging revealed that calcium homeostasis was initially preserved in this 'acute axonal beading' state, ruling out disruption of the axonal membrane, which sets this form of axon injury apart from previously described forms of traumatic and inflammatory axon damage. Morphological, pharmacological and genetic analyses showed that AQP4-IgG-induced axon injury involved osmotic stress and ionic overload, but does not appear to use canonical pathways of Wallerian-like degeneration. Subcellular analysis demonstrated remodelling of the axonal cytoskeleton in beaded axons, especially local loss of microtubules. Treatment with the microtubule stabilizer epothilone, a putative therapy approach for traumatic and degenerative axonopathies, prevented axonal beading, while destabilizing microtubules sensitized axons for beading. Our results reveal a distinct form of immune-mediated axon pathology in neuromyelitis optica that mechanistically differs from known cascades of post-traumatic and inflammatory axon loss, and suggest a new strategy for neuroprotection in neuromyelitis optica and related diseases.
MeSH term(s)	Animals ; Aquaporin 4 ; Astrocytes/metabolism ; Autoantibodies/metabolism ; Axons/pathology ; Humans ; Immunoglobulin G/metabolism ; Mice ; Neuromyelitis Optica/metabolism
Chemical Substances	Aquaporin 4 ; Autoantibodies ; Immunoglobulin G
Language	English
Publishing date	2024-02-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awac079
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.26: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Author Correction: Spatial proteomics reveals secretory pathway disturbances caused by neuropathy-associated TECPR2.

Nalbach, Karsten / Schifferer, Martina / Bhattacharya, Debjani / Ho-Xuan, Hung / Tseng, Wei Chou / Williams, Luis A / Stolz, Alexandra / Lichtenthaler, Stefan F / Elazar, Zvulun / Behrends, Christian

Nature communications

2023 Volume 14, Issue 1, Page(s) 8322

Language	English
Publishing date	2023-12-14
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43990-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Systematically defining selective autophagy receptor-specific cargo using autophagosome content profiling

Zellner, Susanne / Schifferer, Martina / Behrends, Christian

Molecular cell. 2021 Mar. 18, v. 81, no. 6

2021

Abstract	Autophagy deficiency in fed conditions leads to the formation of protein inclusions highlighting the contribution of this lysosomal delivery route to cellular proteostasis. Selective autophagy pathways exist that clear accumulated and aggregated ubiquitinated proteins. Receptors for this type of autophagy (aggrephagy) include p62, NBR1, TOLLIP, and OPTN, which possess LC3-interacting regions and ubiquitin-binding domains (UBDs), thus working as a bridge between LC3/GABARAP proteins and ubiquitinated substrates. However, the identity of aggrephagy substrates and the redundancy of aggrephagy and related UBD-containing receptors remains elusive. Here, we combined proximity labeling and organelle enrichment with quantitative proteomics to systematically map the autophagic degradome targeted by UBD-containing receptors under basal and proteostasis-challenging conditions in human cell lines. We identified various autophagy substrates, some of which were differentially engulfed by autophagosomal and endosomal membranes via p62 and TOLLIP, respectively. Overall, this resource will allow dissection of the proteostasis contribution of autophagy to numerous individual proteins.
Keywords	autophagosomes ; dissection ; humans ; macroautophagy ; proteomics
Language	English
Dates of publication	2021-0318
Size	p. 1337-1354.e8.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2021.01.009
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 2005/501: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging.

Todorov-Völgyi, Katalin / González-Gallego, Judit / Müller, Stephan A / Beaufort, Nathalie / Malik, Rainer / Schifferer, Martina / Todorov, Mihail Ivilinov / Crusius, Dennis / Robinson, Sophie / Schmidt, Andree / Körbelin, Jakob / Bareyre, Florence / Ertürk, Ali / Haass, Christian / Simons, Mikael / Paquet, Dominik / Lichtenthaler, Stefan F / Dichgans, Martin

Nature aging

2024 Volume 4, Issue 4, Page(s) 595–612

Abstract: Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into ... ...

Abstract	Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis revealed a segregation of age-related protein dynamics with biological functions, including a downregulation of vesicle-mediated transport. We found a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis and lysosomal degradation. In gene deletion and overexpression experiments, Arf6 affected endocytosis pathways in endothelial cells. Our approach uncovered changes not picked up by transcriptomic studies, such as accumulation of vesicle cargo and receptor ligands, including Apoe. Proteomic analysis of BECs from Apoe-deficient mice revealed a signature of accelerated aging. Our findings provide a resource for analysing BEC function during aging.
MeSH term(s)	Mice ; Animals ; Endothelial Cells/metabolism ; Proteomics/methods ; Brain/metabolism ; Endothelium/metabolism ; Apolipoproteins E/metabolism
Chemical Substances	Apolipoproteins E
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ISSN	2662-8465
ISSN (online)	2662-8465
DOI	10.1038/s43587-024-00598-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Size-Selective Transfer of Lipid Nanoparticle-Based Drug Carriers Across the Blood Brain Barrier Via Vascular Occlusions Following Traumatic Brain Injury.

Khalin, Igor / Adarsh, Nagappanpillai / Schifferer, Martina / Wehn, Antonia / Groschup, Bernhard / Misgeld, Thomas / Klymchenko, Andrey / Plesnila, Nikolaus

Small (Weinheim an der Bergstrasse, Germany)

2022 Volume 18, Issue 18, Page(s) e2200302

Abstract: The current lack of understanding about how nanocarriers cross the blood-brain barrier (BBB) in the healthy and injured brain is hindering the clinical translation of nanoscale brain-targeted drug-delivery systems. Here, the bio-distribution of lipid ... ...

Abstract	The current lack of understanding about how nanocarriers cross the blood-brain barrier (BBB) in the healthy and injured brain is hindering the clinical translation of nanoscale brain-targeted drug-delivery systems. Here, the bio-distribution of lipid nano-emulsion droplets (LNDs) of two sizes (30 and 80 nm) in the mouse brain after traumatic brain injury (TBI) is investigated. The highly fluorescent LNDs are prepared by loading them with octadecyl rhodamine B and a bulky hydrophobic counter-ion, tetraphenylborate. Using in vivo two-photon and confocal imaging, the circulation kinetics and bio-distribution of LNDs in the healthy and injured mouse brain are studied. It is found that after TBI, LNDs of both sizes accumulate at vascular occlusions, where specifically 30 nm LNDs extravasate into the brain parenchyma and reach neurons. The vascular occlusions are not associated with bleedings, but instead are surrounded by processes of activated microglia, suggesting a specific opening of the BBB. Finally, correlative light-electron microscopy reveals 30 nm LNDs in endothelial vesicles, while 80 nm particles remain in the vessel lumen, indicating size-selective vesicular transport across the BBB via vascular occlusions. The data suggest that microvascular occlusions serve as "gates" for the transport of nanocarriers across the BBB.
MeSH term(s)	Animals ; Blood-Brain Barrier ; Brain ; Brain Injuries, Traumatic ; Drug Carriers/chemistry ; Liposomes ; Mice ; Nanoparticles/chemistry
Chemical Substances	Drug Carriers ; Lipid Nanoparticles ; Liposomes
Language	English
Publishing date	2022-04-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2168935-0
ISSN	1613-6829 ; 1613-6810
ISSN (online)	1613-6829
ISSN	1613-6810
DOI	10.1002/smll.202200302
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex.

Mezydlo, Aleksandra / Treiber, Nils / Ullrich Gavilanes, Emily Melisa / Eichenseer, Katharina / Ancău, Mihai / Wens, Adinda / Ares Carral, Carla / Schifferer, Martina / Snaidero, Nicolas / Misgeld, Thomas / Kerschensteiner, Martin

Neuron

2023 Volume 111, Issue 11, Page(s) 1748–1759.e8

Abstract: In multiple sclerosis, an inflammatory attack results in myelin loss, which can be partially reversed by remyelination. Recent studies suggest that mature oligodendrocytes could contribute to remyelination by generating new myelin. Here, we show that in ... ...

Abstract	In multiple sclerosis, an inflammatory attack results in myelin loss, which can be partially reversed by remyelination. Recent studies suggest that mature oligodendrocytes could contribute to remyelination by generating new myelin. Here, we show that in a mouse model of cortical multiple sclerosis pathology, surviving oligodendrocytes can indeed extend new proximal processes but rarely generate new myelin internodes. Furthermore, drugs that boost myelin recovery by targeting oligodendrocyte precursor cells did not enhance this alternate mode of myelin regeneration. These data indicate that the contribution of surviving oligodendrocytes to myelin recovery in the inflamed mammalian CNS is minor and inhibited by distinct remyelination brakes.
MeSH term(s)	Mice ; Animals ; Remyelination ; Oligodendroglia/pathology ; Myelin Sheath/pathology ; Multiple Sclerosis ; Axons/pathology ; Mammals
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2023.03.031
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Ganglioside lipidomics of CNS myelination using direct infusion shotgun mass spectrometry.

Arends, Martina / Weber, Melanie / Papan, Cyrus / Damm, Markus / Surma, Michal A / Spiegel, Christopher / Djannatian, Minou / Li, Shengrong / Connell, Lisa / Johannes, Ludger / Schifferer, Martina / Klose, Christian / Simons, Mikael

iScience

2022 Volume 25, Issue 11, Page(s) 105323

Abstract: Gangliosides are present and concentrated in axons and implicated in axon-myelin interactions, but how ganglioside composition changes during myelin formation is not known. Here, we present a direct infusion (shotgun) lipidomics method to analyze ... ...

Abstract	Gangliosides are present and concentrated in axons and implicated in axon-myelin interactions, but how ganglioside composition changes during myelin formation is not known. Here, we present a direct infusion (shotgun) lipidomics method to analyze gangliosides in small amounts of tissue reproducibly and with high sensitivity. We resolve the mouse ganglioside lipidome during development and adulthood and determine the ganglioside content of mice lacking the
Language	English
Publishing date	2022-10-10
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105323
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Membrane lipid remodeling modulates γ-secretase processivity.

Dawkins, Edgar / Derks, Rico J E / Schifferer, Martina / Trambauer, Johannes / Winkler, Edith / Simons, Mikael / Paquet, Dominik / Giera, Martin / Kamp, Frits / Steiner, Harald

The Journal of biological chemistry

2023 Volume 299, Issue 4, Page(s) 103027

Abstract: Imbalances in the amounts of amyloid-β peptides (Aβ) generated by the membrane proteases β- and γ-secretase are considered as a trigger of Alzheimer's disease (AD). Cell-free studies of γ-secretase have shown that increasing membrane thickness modulates ... ...

Abstract	Imbalances in the amounts of amyloid-β peptides (Aβ) generated by the membrane proteases β- and γ-secretase are considered as a trigger of Alzheimer's disease (AD). Cell-free studies of γ-secretase have shown that increasing membrane thickness modulates Aβ generation but it has remained unclear if these effects are translatable to cells. Here we show that the very long-chain fatty acid erucic acid (EA) triggers acyl chain remodeling in AD cell models, resulting in substantial lipidome alterations which included increased esterification of EA in membrane lipids. Membrane remodeling enhanced γ-secretase processivity, resulting in the increased production of the potentially beneficial Aβ37 and/or Aβ38 species in multiple cell lines. Unexpectedly, we found that the membrane remodeling stimulated total Aβ secretion by cells expressing WT γ-secretase but lowered it for cells expressing an aggressive familial AD mutant γ-secretase. We conclude that EA-mediated modulation of membrane composition is accompanied by complex lipid homeostatic changes that can impact amyloidogenic processing in different ways and elicit distinct γ-secretase responses, providing critical implications for lipid-based AD treatment strategies.
MeSH term(s)	Humans ; Amyloid Precursor Protein Secretases/genetics ; Amyloid Precursor Protein Secretases/metabolism ; Membrane Lipids/metabolism ; Amyloid beta-Peptides/metabolism ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Cell Line ; Amyloid beta-Protein Precursor/metabolism ; Presenilin-1/metabolism
Chemical Substances	Amyloid Precursor Protein Secretases (EC 3.4.-) ; Membrane Lipids ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Presenilin-1
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.103027
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.108: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito