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Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis

Boland, Sebastian ; Swarup, Sharan ; Ambaw, Yohannes A. ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Nature Communications Vol. 13, No. 1 ( 2022-10-07)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-10-07)

Abstract: Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN -mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/s41467-022-33500-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2553671-0

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Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast

de Godoy, Lyris M. F. ; Olsen, Jesper V. ; Cox, Jürgen ; [et al.]

Springer Science and Business Media LLC ; 2008

In: Nature Vol. 455, No. 7217 ( 2008-10), p. 1251-1254

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In: Nature, Springer Science and Business Media LLC, Vol. 455, No. 7217 ( 2008-10), p. 1251-1254

Type of Medium: Online Resource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/nature07341

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WA 15000

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2008

detail.hit.zdb_id: 120714-3

detail.hit.zdb_id: 1413423-8

SSG: 11

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Wissenschaftspark Albert Einstein

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TH Wildau

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The Lipid Droplet Knowledge Portal: A resource for systematic analyses of lipid droplet biology

Mejhert, Niklas ; Gabriel, Katlyn R. ; Frendo-Cumbo, Scott ; [et al.]

Elsevier BV ; 2022

In: Developmental Cell Vol. 57, No. 3 ( 2022-02), p. 387-397.e4

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In: Developmental Cell, Elsevier BV, Vol. 57, No. 3 ( 2022-02), p. 387-397.e4

Type of Medium: Online Resource

ISSN: 1534-5807

URL: Article

DOI: 10.1016/j.devcel.2022.01.003

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2053870-4

SSG: 12

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Linear Mitochondrial Plasmids of F. oxysporum Are Novel, Telomere-like Retroelements

Walther, Tobias C ; Kennell, John C

Elsevier BV ; 1999

In: Molecular Cell Vol. 4, No. 2 ( 1999-08), p. 229-238

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In: Molecular Cell, Elsevier BV, Vol. 4, No. 2 ( 1999-08), p. 229-238

Type of Medium: Online Resource

ISSN: 1097-2765

URL: Article

DOI: 10.1016/S1097-2765(00)80370-6

Language: English

Publisher: Elsevier BV

Publication Date: 1999

detail.hit.zdb_id: 2001948-8

SSG: 12

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An open-access volume electron microscopy atlas of whole cells and tissues

Xu, C. Shan ; Pang, Song ; Shtengel, Gleb ; [et al.]

Springer Science and Business Media LLC ; 2021

In: Nature Vol. 599, No. 7883 ( 2021-11-04), p. 147-151

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In: Nature, Springer Science and Business Media LLC, Vol. 599, No. 7883 ( 2021-11-04), p. 147-151

Type of Medium: Online Resource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-021-03992-4

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Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 120714-3

detail.hit.zdb_id: 1413423-8

SSG: 11

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A Role for Phosphatidic Acid in the Formation of “Supersized” Lipid Droplets

Fei, Weihua ; Shui, Guanghou ; Zhang, Yuxi ; [et al.]

Public Library of Science (PLoS) ; 2011

In: PLoS Genetics Vol. 7, No. 7 ( 2011-7-28), p. e1002201-

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In: PLoS Genetics, Public Library of Science (PLoS), Vol. 7, No. 7 ( 2011-7-28), p. e1002201-

Type of Medium: Online Resource

ISSN: 1553-7404

URL: Article

DOI: 10.1371/journal.pgen.1002201

DOI: 10.1371/journal.pgen.1002201.g001

DOI: 10.1371/journal.pgen.1002201.g002

DOI: 10.1371/journal.pgen.1002201.g003

DOI: 10.1371/journal.pgen.1002201.g004

DOI: 10.1371/journal.pgen.1002201.g005

DOI: 10.1371/journal.pgen.1002201.g006

DOI: 10.1371/journal.pgen.1002201.g007

DOI: 10.1371/journal.pgen.1002201.g008

DOI: 10.1371/journal.pgen.1002201.g009

DOI: 10.1371/journal.pgen.1002201.t001

DOI: 10.1371/journal.pgen.1002201.s001

DOI: 10.1371/journal.pgen.1002201.s002

DOI: 10.1371/journal.pgen.1002201.s003

DOI: 10.1371/journal.pgen.1002201.s004

DOI: 10.1371/journal.pgen.1002201.s005

DOI: 10.1371/journal.pgen.1002201.s006

DOI: 10.1371/journal.pgen.1002201.s007

DOI: 10.1371/journal.pgen.1002201.s008

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2011

detail.hit.zdb_id: 2186725-2

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The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets

Chung, Jeeyun ; Park, Joongkyu ; Lai, Zon Weng ; [et al.]

Springer Science and Business Media LLC ; 2023

In: Nature Cell Biology Vol. 25, No. 8 ( 2023-08), p. 1101-1110

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In: Nature Cell Biology, Springer Science and Business Media LLC, Vol. 25, No. 8 ( 2023-08), p. 1101-1110

Abstract: Lipid droplets (LDs) are crucial organelles for energy storage and lipid homeostasis. Autophagy of LDs is an important pathway for their catabolism, but the molecular mechanisms mediating LD degradation by selective autophagy (lipophagy) are unknown. Here we identify spartin as a receptor localizing to LDs and interacting with core autophagy machinery, and we show that spartin is required to deliver LDs to lysosomes for triglyceride mobilization. Mutations in SPART (encoding spartin) lead to Troyer syndrome, a form of complex hereditary spastic paraplegia 1 . Interfering with spartin function in cultured human neurons or murine brain neurons leads to LD and triglyceride accumulation. Our identification of spartin as a lipophagy receptor, thus, suggests that impaired LD turnover contributes to Troyer syndrome development.

Type of Medium: Online Resource

ISSN: 1465-7392 , 1476-4679

URL: Article

DOI: 10.1038/s41556-023-01178-w

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 1494945-3

SSG: 12

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EUV Frankfurt

TH Wildau

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Publisher Correction: An open-access volume electron microscopy atlas of whole cells and tissues

Xu, C. Shan ; Pang, Song ; Shtengel, Gleb ; [et al.]

Springer Science and Business Media LLC ; 2021

In: Nature Vol. 599, No. 7885 ( 2021-11-18), p. E5-E5

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In: Nature, Springer Science and Business Media LLC, Vol. 599, No. 7885 ( 2021-11-18), p. E5-E5

Type of Medium: Online Resource

ISSN: 0028-0836 , 1476-4687

URL: Article

DOI: 10.1038/s41586-021-04132-8

RVK:

TA 1000

RVK:

UA 1000

RVK:

WA 15000

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 120714-3

detail.hit.zdb_id: 1413423-8

SSG: 11

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Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation

Siragusa, Mauro ; Fröhlich, Florian ; Park, Eon Joo ; [et al.]

American Association for the Advancement of Science (AAAS) ; 2015

In: Science Signaling Vol. 8, No. 390 ( 2015-08-18)

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In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 8, No. 390 ( 2015-08-18)

Abstract: Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l -arginine and molecular oxygen into l -citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell–derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser 1177 , a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser 1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells.

Type of Medium: Online Resource

ISSN: 1945-0877 , 1937-9145

URL: Article

DOI: 10.1126/scisignal.aaa2819

Language: English

Publisher: American Association for the Advancement of Science (AAAS)

Publication Date: 2015

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The Endoplasmic Reticulum Enzyme DGAT2 Is Found in Mitochondria-associated Membranes and Has a Mitochondrial Targeting Signal That Promotes Its Association with Mitochondria

Stone, Scot J. ; Levin, Malin C. ; Zhou, Ping ; [et al.]

Elsevier BV ; 2009

In: Journal of Biological Chemistry Vol. 284, No. 8 ( 2009-02), p. 5352-5361

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In: Journal of Biological Chemistry, Elsevier BV, Vol. 284, No. 8 ( 2009-02), p. 5352-5361

Type of Medium: Online Resource

ISSN: 0021-9258

URL: Article

DOI: 10.1074/jbc.M805768200

Language: English

Publisher: Elsevier BV

Publication Date: 2009

detail.hit.zdb_id: 2141744-1

detail.hit.zdb_id: 1474604-9

SSG: 12

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BTU Cottbus

Wissenschaftspark Albert Einstein

EUV Frankfurt

TH Wildau

FH Potsdam

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