Research ExplorerPublicationsAnnexin A6 modulates TBC1D15/Rab7/StARD3 axis to control end...

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

Standard

Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells. / Meneses-Salas, Elsa; García-Melero, Ana; Kanerva, Kristiina; Blanco-Muñoz, Patricia; Morales-Paytuvi, Frederic; Bonjoch, Júlia; Casas, Josefina; Egert, Antonia; Beevi, Syed S; Jose, Jaimy; Llorente-Cortés, Vicenta; Rye, Kerry-Anne; Heeren, Joerg; Lu, Albert; Pol, Albert; Tebar, Francesc; Ikonen, Elina; Grewal, Thomas; Enrich, Carlos; Rentero, Carles.

In: CELL MOL LIFE SCI, Vol. 77, No. 14, 07.2020, p. 2839-2857.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Meneses-Salas, E, García-Melero, A, Kanerva, K, Blanco-Muñoz, P, Morales-Paytuvi, F, Bonjoch, J, Casas, J, Egert, A, Beevi, SS, Jose, J, Llorente-Cortés, V, Rye, K-A, Heeren, J, Lu, A, Pol, A, Tebar, F, Ikonen, E, Grewal, T, Enrich, C & Rentero, C 2020, 'Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells', CELL MOL LIFE SCI, vol. 77, no. 14, pp. 2839-2857. https://doi.org/10.1007/s00018-019-03330-y

APA

Meneses-Salas, E., García-Melero, A., Kanerva, K., Blanco-Muñoz, P., Morales-Paytuvi, F., Bonjoch, J., Casas, J., Egert, A., Beevi, S. S., Jose, J., Llorente-Cortés, V., Rye, K-A., Heeren, J., Lu, A., Pol, A., Tebar, F., Ikonen, E., Grewal, T., Enrich, C., & Rentero, C. (2020). Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells. CELL MOL LIFE SCI, 77(14), 2839-2857. https://doi.org/10.1007/s00018-019-03330-y

Vancouver

Meneses-Salas E, García-Melero A, Kanerva K, Blanco-Muñoz P, Morales-Paytuvi F, Bonjoch J et al. Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells. CELL MOL LIFE SCI. 2020 Jul;77(14):2839-2857. https://doi.org/10.1007/s00018-019-03330-y

Bibtex

@article{e4c4304bce5d4f6f8e2b9f94506a8a1a,
title = "Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells",
abstract = "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 = "Animals, Annexin A6/genetics, CHO Cells, Carrier Proteins/genetics, Cell Membrane/genetics, Cholesterol/genetics, Cricetulus, Endoplasmic Reticulum/genetics, Endosomes/genetics, GTPase-Activating Proteins/genetics, Humans, Membrane Proteins/genetics, Niemann-Pick Disease, Type C/genetics, Protein Domains/genetics, Protein Transport/genetics, RNA, Small Interfering/genetics, rab GTP-Binding Proteins/genetics",
author = "Elsa Meneses-Salas and Ana Garc{\'i}a-Melero and Kristiina Kanerva and Patricia Blanco-Mu{\~n}oz and Frederic Morales-Paytuvi and J{\'u}lia Bonjoch and Josefina Casas and Antonia Egert and Beevi, {Syed S} and Jaimy Jose and Vicenta Llorente-Cort{\'e}s and Kerry-Anne Rye and Joerg Heeren and Albert Lu and Albert Pol and Francesc Tebar and Elina Ikonen and Thomas Grewal and Carlos Enrich and Carles Rentero",
year = "2020",
month = jul,
doi = "10.1007/s00018-019-03330-y",
language = "English",
volume = "77",
pages = "2839--2857",
journal = "CELL MOL LIFE SCI",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "14",

}

RIS

TY - JOUR

T1 - Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells

AU - Meneses-Salas, Elsa

AU - García-Melero, Ana

AU - Kanerva, Kristiina

AU - Blanco-Muñoz, Patricia

AU - Morales-Paytuvi, Frederic

AU - Bonjoch, Júlia

AU - Casas, Josefina

AU - Egert, Antonia

AU - Beevi, Syed S

AU - Jose, Jaimy

AU - Llorente-Cortés, Vicenta

AU - Rye, Kerry-Anne

AU - Heeren, Joerg

AU - Lu, Albert

AU - Pol, Albert

AU - Tebar, Francesc

AU - Ikonen, Elina

AU - Grewal, Thomas

AU - Enrich, Carlos

AU - Rentero, Carles

PY - 2020/7

Y1 - 2020/7

N2 - 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.

AB - 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.

KW - Animals

KW - Annexin A6/genetics

KW - CHO Cells

KW - Carrier Proteins/genetics

KW - Cell Membrane/genetics

KW - Cholesterol/genetics

KW - Cricetulus

KW - Endoplasmic Reticulum/genetics

KW - Endosomes/genetics

KW - GTPase-Activating Proteins/genetics

KW - Humans

KW - Membrane Proteins/genetics

KW - Niemann-Pick Disease, Type C/genetics

KW - Protein Domains/genetics

KW - Protein Transport/genetics

KW - RNA, Small Interfering/genetics

KW - rab GTP-Binding Proteins/genetics

U2 - 10.1007/s00018-019-03330-y

DO - 10.1007/s00018-019-03330-y

M3 - SCORING: Journal article

C2 - 31664461

VL - 77

SP - 2839

EP - 2857

JO - CELL MOL LIFE SCI

JF - CELL MOL LIFE SCI

SN - 1420-682X

IS - 14

ER -