Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment

Abstract Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartm...

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Autores principales: Naomi Matsumoto, Mizuki Sekiya, Koujiro Tohyama, Eri Ishiyama-Matsuura, Ge-Hong Sun-Wada, Yoh Wada, Masamitsu Futai, Mayumi Nakanishi-Matsui
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/3d1d5a34a2cd40518eac163e08643f18
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spelling oai:doaj.org-article:3d1d5a34a2cd40518eac163e08643f182021-12-02T11:40:46ZEssential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment10.1038/s41598-018-24918-72045-2322https://doaj.org/article/3d1d5a34a2cd40518eac163e08643f182018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24918-7https://doaj.org/toc/2045-2322Abstract Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartment, providing optimal conditions for bone resorption. However, little is known about the mechanism underlying this trafficking of secretory lysosomes. Here, we demonstrate that the lysosome-specific a3 isoform of the V-ATPase a subunit plays an indispensable role in secretory lysosome trafficking, together with Rab7, a small GTPase involved in organelle trafficking. In osteoclasts lacking a3, lysosomes were not transported to the cell periphery, and Rab7 was not localised to lysosomes but diffused throughout the cytoplasm. Expression of dominant-negative (GDP-bound form) Rab7 inhibited lysosome trafficking in wild-type cells. Furthermore, a3 directly interacted with the GDP-bound forms of Rab7 and Rab27A. These findings reveal a novel role for the proton pump V-ATPase in secretory lysosome trafficking and an unexpected mechanistic link with Rab GTPases.Naomi MatsumotoMizuki SekiyaKoujiro TohyamaEri Ishiyama-MatsuuraGe-Hong Sun-WadaYoh WadaMasamitsu FutaiMayumi Nakanishi-MatsuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-18 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Naomi Matsumoto
Mizuki Sekiya
Koujiro Tohyama
Eri Ishiyama-Matsuura
Ge-Hong Sun-Wada
Yoh Wada
Masamitsu Futai
Mayumi Nakanishi-Matsui
Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment
description Abstract Secretory lysosomes are required for the specialised functions of various types of differentiated cells. In osteoclasts, the lysosomal proton pump V-ATPase (vacuolar-type ATPase) is targeted to the plasma membrane via secretory lysosomes and subsequently acidifies the extracellular compartment, providing optimal conditions for bone resorption. However, little is known about the mechanism underlying this trafficking of secretory lysosomes. Here, we demonstrate that the lysosome-specific a3 isoform of the V-ATPase a subunit plays an indispensable role in secretory lysosome trafficking, together with Rab7, a small GTPase involved in organelle trafficking. In osteoclasts lacking a3, lysosomes were not transported to the cell periphery, and Rab7 was not localised to lysosomes but diffused throughout the cytoplasm. Expression of dominant-negative (GDP-bound form) Rab7 inhibited lysosome trafficking in wild-type cells. Furthermore, a3 directly interacted with the GDP-bound forms of Rab7 and Rab27A. These findings reveal a novel role for the proton pump V-ATPase in secretory lysosome trafficking and an unexpected mechanistic link with Rab GTPases.
format article
author Naomi Matsumoto
Mizuki Sekiya
Koujiro Tohyama
Eri Ishiyama-Matsuura
Ge-Hong Sun-Wada
Yoh Wada
Masamitsu Futai
Mayumi Nakanishi-Matsui
author_facet Naomi Matsumoto
Mizuki Sekiya
Koujiro Tohyama
Eri Ishiyama-Matsuura
Ge-Hong Sun-Wada
Yoh Wada
Masamitsu Futai
Mayumi Nakanishi-Matsui
author_sort Naomi Matsumoto
title Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment
title_short Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment
title_full Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment
title_fullStr Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment
title_full_unstemmed Essential Role of the a3 Isoform of V-ATPase in Secretory Lysosome Trafficking via Rab7 Recruitment
title_sort essential role of the a3 isoform of v-atpase in secretory lysosome trafficking via rab7 recruitment
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/3d1d5a34a2cd40518eac163e08643f18
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