Annexins—Coordinators of Cholesterol Homeostasis in Endocytic Pathways

Rentero, Carles; Blanco‐Muñoz, Patricia; Meneses‐Salas, Elsa; Grewal, Thomas; Enrich, Carlos

doi:10.3390/ijms19051444

Cited by 53 publications

(53 citation statements)

References 213 publications

(344 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Depletion of AnxA6 could stabilize StARD3/VAP-A and Rab7/protrudin/VAP-A complexes, ensuring re-establishment of MCS between the ER and late endosomes, and eventually the transfer of late endosome-cholesterol to the ER in cells with non-functional NPC1. Although several annexins contribute to endosomal membrane dynamics [62,96,97], only the AnxA1/S100A11 protein complex has yet been associated with MCS formation [90]. While AnxA2 and AnxA6 are also well known to bind S100 proteins, to our knowledge there is no data linking AnxA2 with MCS [90,98].…”

Section: Discussionmentioning

confidence: 92%

“…We previously demonstrated that AnxA6 overexpression led to late endosome-cholesterol accumulation, a phenotype reminiscent of the NPC1 mutant phenotype [46,62]. This was accompanied by an increased recruitment of AnxA6 to cholesterol-laden late endosomes upon pharmacological NPC1 inhibition, using U18666A, or loading with LDL [43][44][45].…”

Section: Interaction Of Anxa6 With the Rab7-gap Tbc1d15mentioning

confidence: 94%

See 1 more Smart Citation

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

Meneses‐Salas

García-Melero

Kanerva

et al. 2019

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation. Keywords Cholesterol • Late endosomes • Rab7 • NPC1 • Annexin A6 • Membrane contact sites Abbreviations A431 Human epidermoid carcinoma cells ACAT Acyl-CoA:cholesterol acyltransferase AnxA6 Annexin A6 CHO Chinese hamster ovary CHO M12 NPC1 mutant CHO cell line CMA Chaperone-mediated autophagy ER Endoplasmic reticulum FYCO1 FYVE and coiled-coil domain containing 1 GST Glutathione S-transferase LE/Lys Late endosome/lysosome (endolysosomes) LPDS Lipoprotein-deficient serum MCS Membrane contact sites MEF Mouse embryonic fibroblasts MOSPD2 Motile sperm domain containing 2 NPC1 Niemann-Pick type C1 ORP1L Oxysterol-related protein 1L OSBP Oxysterol-binding protein PFO Perfringolysin O RILP Rab interacting lysosomal protein SREBP Sterol regulatory element binding protein StARD3 StAR-related lipid transfer domain-3 TBC1D15 TBC1 domain family member 15 WT Wild type VAP-A Vesicle-associated membrane protein-associated protein A Vps13 Vacuolar protein sorting-associated protein 13 Cellular and Molecular Life Sciences Elsa Meneses-Salas and Ana García-Melero contributed equally to this work.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Interaction Of Anxa6 With the Rab7-gap Tbc1d15mentioning

confidence: 94%

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

Meneses‐Salas

García-Melero

Kanerva

et al. 2019

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both ANXA1 and ANXA2 are DEGs in the F8FvsF4F group and they were all highly expressed at four weeks of age in the study. Annexin (ANX) is a kind of protein superfamily with high abundance, calcium-dependent, and binding to negatively charged membrane phospholipids (Rentero et al, 2018;Xie et al, 2018). One of the driving forces underlying cell migration and intercellular interactions is the reorganization of cell membranes and remodeling of the cytoskeleton, processes facilitated by Annexin proteins in multiple systems (Shah, Schiffmacher & Taneyhill, 2017).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome for the breast muscle of Jinghai yellow chicken at early growth stages

Zhang

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background. The meat quality of yellow feathered broilers is better than the quality of its production. Growth traits are important in the broiler industry. The exploration of regulation mechanisms for the skeletal muscle would help to increase the growth performance of chickens. At present, some progress has been made by researchers, but the molecular mechanisms of the skeletal muscle still remain unclear and need to be improved. Methods. In this study, the breast muscles of fast-and slow-growing female Jinghai yellow chickens (F4F, F8F, F4S, F8S) and slow-growing male Jinghai yellow chickens (M4S, M8S) aged four and eight weeks were selected for transcriptome sequencing (RNA-seq). All analyses of differentially expressed genes (DEGs) and functional enrichment were performed. Finally, we selected nine DEGs to verify the accuracy of the sequencing by qPCR. Results. The differential gene expression analysis resulted in 364, 219 and 111 DEGs (adjusted P-value ≤ 0.05) for the three comparison groups, F8FvsF4F, F8SvsF4S, and M8SvsM4S, respectively. Three common DEGs (ADAMTS20, ARHGAP19, and Novel00254) were found, and they were all highly expressed at four weeks of age. In addition, some other genes related to growth and development, such as ANXA1, COL1A1, MYH15, TGFB3 and ACTC1, were obtained. The most common DEGs (n = 58) were found between the two comparison groups F8FvsF4F and F8SvsF4S, and they might play important roles in the growth of female chickens. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway also showed some significant enrichment pathways, for instance, extracellular matrix (ECM)-receptor interaction, focal adhesion, cell cycle, and DNA replication. The two pathways that were significantly enriched in the F8FvsF4F group were all contained in that of F8SvsF4S. The same two pathways were ECM-receptor interaction and focal adhesion, and they had great influence on the growth of chickens. However, many differences existed between male and female chickens in regards to common DEGs and KEGG pathways. The results would help to reveal the regulation mechanism of the growth and development of chickens and serve as a guideline to propose an experimental design on gene function with the DEGs and pathways. M. 2017. Sound analysis to model weight of broiler chickens. Francisco CL, Jorge AM, Dalpaisilva M, Carani FR, Cabeço LC, Silva SR. 2011. Muscle fiber type characterization and myosin heavy chain (MyHC) isoform expression in Mediterranean buffaloes. Meat Science 88(3):535-541 DOI 10.1016/j.meatsci.2011.02.007. Friedrich RE, Scheuer HA, Holtje W. 2019. The effect of bisphosphonate medication on orthodontics and orthognathic surgery in patients with osteogenesis imperfecta. GMS Interdisciplinary Plastic and Reconstructive Surgery DGPW 8:Doc06 . 2019. Synergistic effects of recombinant Lentiviral-mediated BMP2 and TGF-beta3 on the osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro. Cytokine 120:1-8 Noda M. 2016. Collagens VI and XII form complexes mediating osteoblast interact...

show abstract

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Transcriptome for the breast muscle of Jinghai yellow chicken at early growth stages (v0.1)"

2020

View full text Add to dashboard Cite

Background: The meat quality of yellow feathered broilers is better than the quality of its production. Growth traits are important in the broiler industry. The exploration of regulation mechanisms for the skeletal muscle would help to increase the growth performance of chickens. At present, some progress has been made by researchers, but the molecular mechanisms of the skeletal muscle still remain unclear and need to be improved. Methods: In this study, the breast muscles of fast-and slow-growing female Jinghai yellow chickens (F4F, F8F, F4S, F8S) and slow-growing male Jinghai yellow chickens (M4S, M8S) aged four and eight weeks were selected for transcriptome sequencing (RNAseq). All analyses of differentially expressed genes (DEGs) and functional enrichment were performed. Finally, we selected nine DEGs to verify the accuracy of the sequencing by qPCR. Results: The differential gene expression analysis resulted in 364, 219 and 111 DEGs (adjusted P-value ≤0.05) for the three comparison groups, F8FvsF4F, F8SvsF4S, and M8SvsM4S, respectively. Three common DEGs (ADAMTS20, ARHGAP19, and Novel00254) were found , and they were all highly expressed at four weeks of age. In addition, some other genes related to growth and development, such as ANXA1, COL1A1, MYH15, TGFB3 and ACTC1, were obtained. The most common DEGs (n =58) were found between the two comparison groups F8FvsF4F and F8SvsF4S, and they might play important roles in the growth of female chickens. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway also showed some significant enrichment pathways, for instance, extracellular matrix (ECM)-receptor interaction, focal adhesion, cell cycle, and DNA replication. The two pathways that were significantly enriched in the F8FvsF4F group were all contained in that of F8SvsF4S. The same two pathways were ECM-receptor interaction and focal adhesion, and they had great influence on the growth of chickens. However, many differences existed between male and female chickens in regards to common DEGs and KEGG pathways. The results would help to reveal the regulation mechanism of the growth and

show abstract

Annexins—Coordinators of Cholesterol Homeostasis in Endocytic Pathways

Cited by 53 publications

References 213 publications

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

Transcriptome for the breast muscle of Jinghai yellow chicken at early growth stages

Peer Review #2 of "Transcriptome for the breast muscle of Jinghai yellow chicken at early growth stages (v0.1)"

Contact Info

Product

Resources

About