SGPL1 stimulates VPS39 recruitment to the mitochondria in MICU1 deficient cells

Jackson, Joshua M.; Wischhof, Lena; Scifo, Enzo; Pellizzer, Anna; Wang, Yiru; Piazzesi, Antonia; Gentile, Debora; Siddig, Sana; Stork, Miriam; Hopkins, Christopher E.; Händler, Kristian; Weis, Joachim; Roos, Andreas; Schultze, Joachim L.; Nicotera, Pierluigi; Ehninger, Dan; Bano, Daniele

doi:10.1016/j.molmet.2022.101503

Cited by 7 publications

(7 citation statements)

References 114 publications

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“…5D and Supplementary table ST 6 ). Using a validated RNAi feeding protocol starting from hatching as described in our previous studies [ 47 , 48 , 51 ], we downregulated F15G9.1, F42H10.3, myo-1 , and tni-4 genes in α-Syn O/E and wsp-1(lof);α-Syn O/E animals (Fig. 6H ).…”

Section: Resultsmentioning

confidence: 99%

“…The following strains were used in this study: wild type N2 (Bristol), BAN419 gas-1(fc21)X;pkIs2386[unc-54p::α-syn::YFP+unc-119( + )] , BAN534 wsp-1(gm324)IV , BAN550 wsp-1(gm324)IV;pkIs2386[unc-54p::α-syn::YFP+unc-119( + )] , BAN686 shEx34[myo-3p::mCherry] , BAN688 pkIs2386[unc-54p::alpha synuclein::YFP + unc-119(+)];shEx34[myo-3p::mCherry] , BAN689 wsp-1(gm324)IV;pkIs2386[unc-54p::alpha synuclein::YFP + unc-119(+)];shEx34[myo-3p::mCherry] , BAN690 shEx1[ges-1p::fat-7 + myo-3p::mCherry] , BAN692 pkIs2386[unc-54p::alpha synuclein::YFP + unc-119(+)];shEx1[ges-1p::fat-7 + myo-3p::mCherry] , BAN693 wsp-1(gm324)IV;pkIs2386[unc-54p::alpha synuclein::YFP + unc-119(+)];shEx1[ges-1p::fat-7 + myo-3p::mCherry] , NL5901 pkIs2386[unc-54p::α-syn::YFP+unc-119(+)] . Nematodes were maintained following standard culture methods as in some of our previous studies [ 47 , 48 , 51 ]. All RNAi experiments were performed at indicated temperatures by feeding nematodes with HT115 E. coli expressing dsRNA against target genes.…”

Section: Methodsmentioning

confidence: 99%

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Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology

Jackson,

Hoffmann,

Scifo

et al. 2024

Cell Death Dis

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Abnormal intraneuronal accumulation of soluble and insoluble α-synuclein (α-Syn) is one of the main pathological hallmarks of synucleinopathies, such as Parkinson’s disease (PD). It has been well documented that the reversible liquid-liquid phase separation of α-Syn can modulate synaptic vesicle condensates at the presynaptic terminals. However, α-Syn can also form liquid-like droplets that may convert into amyloid-enriched hydrogels or fibrillar polymorphs under stressful conditions. To advance our understanding on the mechanisms underlying α-Syn phase transition, we employed a series of unbiased proteomic analyses and found that actin and actin regulators are part of the α-Syn interactome. We focused on Neural Wiskott-Aldrich syndrome protein (N-WASP) because of its association with a rare early-onset familial form of PD. In cultured cells, we demonstrate that N-WASP undergoes phase separation and can be recruited to synapsin 1 liquid-like droplets, whereas it is excluded from α-Syn/synapsin 1 condensates. Consistently, we provide evidence that wsp-1/WASL loss of function alters the number and dynamics of α-Syn inclusions in the nematode Caenorhabditis elegans. Together, our findings indicate that N-WASP expression may create permissive conditions that promote α-Syn condensates and their potentially deleterious conversion into toxic species.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology

Jackson,

Hoffmann,

Scifo

et al. 2024

Cell Death Dis

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“…1E ). Interestingly, the interaction between the TOM complex and VPS39 was previously reported to be essential for the formation of membrane contact sites (MCSs) between cellular vesicles (e.g., endosomes and lysosomes) and mitochondria ( 39 , 40 ). Only recently have MCSs emerged as important host cell structures that enable viruses to reorganize the cellular membranes and channel cell lipids to the growing replication centers ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

CP204L Is a Multifunctional Protein of African Swine Fever Virus That Interacts with the VPS39 Subunit of the Homotypic Fusion and Vacuole Protein Sorting Complex and Promotes Lysosome Clustering

Dolata

Fuchs

Caignard

et al. 2023

J Virol

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“…1E). Interestingly, the interaction between the TOM complex and VPS39 was previously reported to be essential for the formation of membrane contact sites (MCSs) between cellular vesicles (e.g., endosomes, lysosomes) and mitochondria (37, 38). Only recently, MCSs have emerged as important host cell structures that enable viruses to reorganize the cellular membranes and channel cell lipids to the growing replication centers (39, 40).…”

Section: Discussionmentioning

confidence: 99%

CP204L Is a Multifunctional Protein of African Swine Fever Virus That Interacts with The VPS39 Subunit of HOPS Complex and Promotes Lysosome Clustering

Dolata

Fuchs

Caignard

et al. 2022

Preprint

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Virus replication depends on a complex interplay between viral and host proteins. In the case of African swine fever virus (ASFV), a large DNA virus, only few virus-host protein-protein interactions have been identified to date. In this study, we demonstrate that the ASFV protein CP204L directly interacts with the cellular homotypic fusion and protein sorting (HOPS) protein VPS39, blocking its association with the lysosomal HOPS complex, that modulates endolysosomal trafficking and promotes lysosome clustering. Instead, VPS39 is targeted to the sites of virus replication termed virus factories. Furthermore, we show that loss of VPS39 reduces the levels of virus proteins synthesized in the early phase of infection and delays ASFV replication but does not completely inhibit it. Collectively, these results identify a novel virus-host protein interaction that modulates host membrane rearrangement during infection and provide evidence that CP204L is a multifunctional protein engaged in distinct steps of the ASFV life cycle.

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SGPL1 stimulates VPS39 recruitment to the mitochondria in MICU1 deficient cells

Cited by 7 publications

References 114 publications

Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology

Actin-nucleation promoting factor N-WASP influences alpha-synuclein condensates and pathology

CP204L Is a Multifunctional Protein of African Swine Fever Virus That Interacts with the VPS39 Subunit of the Homotypic Fusion and Vacuole Protein Sorting Complex and Promotes Lysosome Clustering

CP204L Is a Multifunctional Protein of African Swine Fever Virus That Interacts with The VPS39 Subunit of HOPS Complex and Promotes Lysosome Clustering

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