Deficiency of the lysosomal exonuclease PLD3 impacts the degradative route

Acker, Zoë P. Van; Bretou, Marine; Sannerud, Ragna; Damme, Markus; Annaert, Wim

doi:10.1002/alz.050868

Cited by 4 publications

(4 citation statements)

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“…Mutations in the 5′-3′ exonuclease PLD3 gene, also known as phospholipase D3, have previously been attributed to patients with late-onset Alzheimer’s disease. − Loss of function leads to increased levels of amyloid beta, which accumulates in the brains of patients with the disease …”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Ghosh,

Neely,

Bland

et al. 2024

J. Proteome Res.

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Section: Discussionmentioning

confidence: 99%

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Ghosh,

Neely,

Bland

et al. 2024

J. Proteome Res.

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“…[35][36][37] Loss of function leads to increased levels of amyloid beta, which accumulates in the brains of patients with the disease. [38]…”

Section: Discussionmentioning

confidence: 99%

“…[35][36] [37] Loss of function leads to increased levels of amyloid beta, which accumulates in the brains of patients with the disease. [38] Calsyntenins bind calcium and play an important role in the production of the amyloid-β peptide by regulating the axonal transport of the amyloid precursor protein. [39] The downregulation of calsyntenin-1 leads to a disruption of axonal transport, which occurs during Alzheimer's disease.…”

Section: Non-dat Vs Dat Candidate Markersmentioning

confidence: 99%

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Ghosh,

Neely,

Bland

et al. 2024

Preprint

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Since 1998, California sea lion (Zalophus californianus) stranding events associated with domoic acid toxicosis have consistently increased. Outside of direct measurement of DA in bodily fluids at the time of stranding, currently there are no practical non-lethal clinical tests for the diagnosis of domoic acid toxicosis (DAT) that can be utilized in a large-scale rehabilitation facility. Proteomic analysis was conducted to discover candidate protein markers of DAT using cerebrospinal fluid from stranded California sea lions with acute DAT (n = 8), chronic DAT (n = 19), or without DAT (n = 13). A total of 2005 protein families were identified experiment-wide (FDR < 0.01). Of these proteins, 83 were significantly different in abundance across the three groups (adj. p < 0.05). Cytoplasmic malate dehydrogenase (MDH1), 5'-3' exonuclease PLD3, disintegrin and metalloproteinase domain-containing protein 22 (ADAM22), 14-3-3 protein gamma (YWHAG), neurosecretory protein VGF, and calsyntenin-1 (CLSTN1) were able to discriminate California sea lions with or without DAT (ROC > 0.75). Immunoglobulin kappa light chain-like (IGKV2D-28), receptor-type tyrosine-phosphatase F (PTRPF), kininogen-1 (KNG1), prothrombin (F2), and beta-synuclein (SNCB) were able to discriminate acute DAT from chronic DAT (ROC > 0.75). Interestingly, proteins involved in alpha synuclein deposition were over-represented as classifiers of DAT and many of these proteins have been implicated in a variety of neurodegenerative diseases. These proteins should be considered potential markers for DAT in California sea lions, as well as markers to discriminate between acute or chronic DAT, and should be considered priority for future validation studies as biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD041356 (http://proteomecentral.proteomexchange.org/dataset/PXD041356).

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“…However, failure of neuronal lysosomes to efficiently degrade nuclear and mitochondrial DNA can also result in STING activation following DNA leakage into the cytoplasm (Lan et al, 2014;Van Acker et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

A STING-CASM-GABARAP Pathway Activates LRRK2 at Lysosomes

Bentley-DeSousa,

Ferguson

2023

Preprint

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Mutations that increase LRRK2 kinase activity have been linked to Parkinson’s disease and Crohn’s disease. LRRK2 is also activated by lysosome damage evoked by chemical and pathogenic stimuli. However, the endogenous cellular mechanisms that control LRRK2 kinase activity are not well understood. In this study, we identify signaling through Stimulator of Interferon Genes (STING) as an upstream activator of LRRK2. This LRRK2 activation occurs via the Conjugation of ATG8 to Single Membranes (CASM) pathway. We furthermore establish that multiple chemical stimuli that perturb lysosomal homeostasis also converge on CASM to activate LRRK2. Although CASM mediates the lipidation of multiple ATG8 protein family members, LRRK2 lysosome recruitment and kinase activation is highly dependent on an interaction with the GABARAP member of this family. Collectively these results define a pathway that integrates multiple stimuli at lysosomes to control the kinase activity of LRRK2. Aberrant activation this pathway may be of relevance in both Parkinson’s and Crohn’s diseases.

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Deficiency of the lysosomal exonuclease PLD3 impacts the degradative route

Cited by 4 publications

References 0 publications

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

Identification of Candidate Protein Biomarkers Associated with Domoic Acid Toxicosis in Cerebrospinal Fluid of California Sea Lions (Zalophus californianus)

A STING-CASM-GABARAP Pathway Activates LRRK2 at Lysosomes

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