2018
DOI: 10.1038/s41590-018-0179-y
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PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing

Abstract: The sensing of microbial genetic material by leukocytes often elicits beneficial pro-inflammatory cytokines, but dysregulated responses can cause severe pathogenesis. Genome-wide association studies have linked the gene encoding phospholipase D3 (PLD3) to Alzheimer's disease and have linked PLD4 to rheumatoid arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins whose functions are obscure. Here, PLD4-deficient mice were found to have an inflammatory disease, marked by elevated levels of i… Show more

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Cited by 97 publications
(142 citation statements)
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References 57 publications
(68 reference statements)
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“…Unique SARS-CoV-2 interactors include FOXK1 and NR2F2, both of which are anti-viral transcription factors induced in response to other viruses 27,28 . We also observe an exonuclease regulator of endosomal nucleic acid sensing (PLD3) 29 , a transcription factor associated with the influenza humoral response (MAZ) 30,31 , and a DNA-binding protein implicated in B cell class switching (KIN or KIN17) 32 . In contrast, the list of unique SARS-CoV-1 interactors includes components of the 4EFP-GYF2 translation repression complex (GYGYF2, EIF4E2), lysosomal ion channels involved in chloride/proton ion exchange (CLCN7, OSTM1), and the cytosolic histone deacetylase 6 (HDAC6).…”
Section: Quantitative Comparison Of Sars-cov-1 and Sars-cov-2 Interacmentioning
confidence: 93%
“…Unique SARS-CoV-2 interactors include FOXK1 and NR2F2, both of which are anti-viral transcription factors induced in response to other viruses 27,28 . We also observe an exonuclease regulator of endosomal nucleic acid sensing (PLD3) 29 , a transcription factor associated with the influenza humoral response (MAZ) 30,31 , and a DNA-binding protein implicated in B cell class switching (KIN or KIN17) 32 . In contrast, the list of unique SARS-CoV-1 interactors includes components of the 4EFP-GYF2 translation repression complex (GYGYF2, EIF4E2), lysosomal ion channels involved in chloride/proton ion exchange (CLCN7, OSTM1), and the cytosolic histone deacetylase 6 (HDAC6).…”
Section: Quantitative Comparison Of Sars-cov-1 and Sars-cov-2 Interacmentioning
confidence: 93%
“…There are a few non-canonical functions of PLDs which include nuclease activity and cardiolipase activity, both of which are mediated by substrate binding at the HKD motif 3,4 . Phospholipase D1 and D2 (PLD1 and PLD2), are confirmed to be enzymatically active mammalian PLD isoforms and are druggable proteins 2,5 .…”
Section: Introductionmentioning
confidence: 99%
“…Spleen samples were prepared as previously described (62). In brief, spleen suspensions were generated by smashing the spleen between frosted glass slides.…”
Section: Flow Cytometry Analysismentioning
confidence: 99%