RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes

Char, Rémy; Liu, Zhuangzhuang; Jacqueline, Cédric; Davieau, Marion; Delgado, Maria–Graciela; Soufflet, Christine; Fallet, Mathieu; Chasson, Lionel; Chapuy, Raphael; Camosseto, Voahirana; Strock, Eva; Rua, Réjane; Almeida, Catarina R.; Su, Bing; Lennon-Duménil, Ana-María; Nal, Béatrice; Roquilly, Antoine; Liang, Yinming; Méresse, Stéphane; Gatti, Evelina; Pierre, Philippe

doi:10.1038/s41467-023-40062-x

Cited by 3 publications

(1 citation statement)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RUFY proteins are structurally similar but functionally different due to unique interaction with Rab GTPase proteins. 21 , 44 For example, RUFY1 is involved in early endosome function through its interactions with Rab4, Rab5, and Rab14, 45 – 47 and RUFY2 plays a role in autophagosome formation via Rab33A/B interaction. 48 , 49 In addition, FYCO1, the RUFY4 paralog, are involved in the fusion of autophagic and endosomal vesicles with lysosomes by interacting with the CCZ1-MON1A complex, which is crucial for Rab7 activation.…”

Section: Discussionmentioning

confidence: 99%

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

Kim,

Park,

et al. 2024

Bone Res

View full text Add to dashboard Cite

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border. However, the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown. Here, we show with GeneChip analysis that RUN and FYVE domain-containing protein 4 (RUFY4) is strongly upregulated during osteoclastogenesis. Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo. Furthermore, deleting Rufy4 did not affect osteoclast differentiation, but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes, their trafficking to the membrane, and their secretion of cathepsin K into the extracellular space. Mechanistically, RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes. Consequently, Rufy4-deficient mice were highly protected from lipopolysaccharide- and ovariectomy-induced bone loss. Thus, RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

show abstract

Section: Discussionmentioning

confidence: 99%

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

Kim,

Park,

et al. 2024

Bone Res

View full text Add to dashboard Cite

show abstract

Peripheral Lysosomal Positioning in Inflamed Odontoblasts Facilitates Mineralization

Xu,

Gao,

Yang

et al. 2024

Journal of Endodontics

View full text Add to dashboard Cite

Single-cell RNA-sequencing identifies unique cell-specific gene expression profiles in high-grade cardiac allograft vasculopathy

Amancherla,

Schlendorf,

Chow

et al. 2024

Preprint

View full text Add to dashboard Cite

BackgroundCardiac allograft vasculopathy (CAV), a diffuse thickening of the intima of the coronary arteries and microvasculature, is the leading cause of late graft failure and mortality after heart transplantation (HT). Diagnosis involves invasive coronary angiography, which carries substantial risk, and minimally-invasive approaches to CAV diagnosis are urgently needed. Using single-cell RNA-sequencing in peripheral blood mononuclear cells (PBMCs), we sought to identify cell-specific gene expression profiles in CAV.MethodsWhole blood was collected from 22 HT recipients with angiographically-confirmed CAV and 18 HT recipients without CAV. PBMCs were isolated and subjected to single-cell RNA-sequencing using a 10X Genomics microfluidic platform. Downstream analyses focused on differential expression of genes, cell compositional changes, and T cell receptor repertoire analyses.ResultsAcross 40 PBMC samples, we isolated 134,984 cells spanning 8 major clusters and 31 subclusters of cell types. Compositional analyses showed subtle, but significant increases in CD4+ T central memory cells, and CD14+ and CD16+ monocytes in high-grade CAV (CAV-2 and CAV-3) as compared to low-grade or absent CAV. After adjusting for age, gender, and prednisone use, 745 genes were differentially expressed in a cell-specific manner in high-grade CAV. Weighted gene co-expression network analyses showed enrichment for putative pathways involved in inflammation and angiogenesis. There were no significant differences in T cell clonality or diversity with increasing CAV severity.ConclusionsUnbiased whole transcriptomic analyses at single-cell resolution identify unique, cell-specific gene expression patterns in CAV, suggesting the potential utility of peripheral gene expression biomarkers in diagnosing CAV.

show abstract

RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes

Cited by 3 publications

References 72 publications

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

Peripheral Lysosomal Positioning in Inflamed Odontoblasts Facilitates Mineralization

Single-cell RNA-sequencing identifies unique cell-specific gene expression profiles in high-grade cardiac allograft vasculopathy

Contact Info

Product

Resources

About