Cargando…

Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages

Both the biogenesis and functions of osteoclasts and macrophages involves dynamic membrane traffic. We screened transcript levels for Rab family small GTPases related to osteoclasts and identified Rab38. Rab38 expression is upregulated during osteoclast differentiation and maturation. In osteoclasts...

Descripción completa

Detalles Bibliográficos
Autores principales: Noda, Kazuya, Lu, Shiou-Ling, Chen, Siyu, Tokuda, Kanako, Li, Yangjie, Hao, Feike, Wada, Yoh, Sun-Wada, Ge-Hong, Murakami, Shinya, Fukuda, Mitsunori, Itoh, Takashi, Noda, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518718/
https://www.ncbi.nlm.nih.gov/pubmed/37625588
http://dx.doi.org/10.1016/j.jbc.2023.105191
_version_ 1785109577168060416
author Noda, Kazuya
Lu, Shiou-Ling
Chen, Siyu
Tokuda, Kanako
Li, Yangjie
Hao, Feike
Wada, Yoh
Sun-Wada, Ge-Hong
Murakami, Shinya
Fukuda, Mitsunori
Itoh, Takashi
Noda, Takeshi
author_facet Noda, Kazuya
Lu, Shiou-Ling
Chen, Siyu
Tokuda, Kanako
Li, Yangjie
Hao, Feike
Wada, Yoh
Sun-Wada, Ge-Hong
Murakami, Shinya
Fukuda, Mitsunori
Itoh, Takashi
Noda, Takeshi
author_sort Noda, Kazuya
collection PubMed
description Both the biogenesis and functions of osteoclasts and macrophages involves dynamic membrane traffic. We screened transcript levels for Rab family small GTPases related to osteoclasts and identified Rab38. Rab38 expression is upregulated during osteoclast differentiation and maturation. In osteoclasts, both Rab38 and its paralog, Rab32, colocalize to lysosome-related organelles (LROs). In macrophages, Rab32 is also found in LROs. LROs are part of the endocytic pathway but are distinct from lysosomes. After receptor activator of NF-κB ligand stimulation, LROs contain cathepsin K and tartrate-resistant acid phosphatase inside and help both proteins to accumulate around bone resorption pits. After osteoclast maturation, these enzymes are hardly found within LROs. In macrophages derived from Rab32 and Rab38 double knockout mice, both acidification and V-ATPase a3 localization were severely compromised. Both the double knockout macrophage and bafilomycin-treated wildtype macrophage show an increase in Lamp1-positive organelles, implying that biogenesis of lysosomes and LROs are related. These results indicate that Rab32 and Rab38 both play a crucial role in LRO biogenesis in macrophages and in osteoclasts.
format Online
Article
Text
id pubmed-10518718
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-105187182023-09-26 Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages Noda, Kazuya Lu, Shiou-Ling Chen, Siyu Tokuda, Kanako Li, Yangjie Hao, Feike Wada, Yoh Sun-Wada, Ge-Hong Murakami, Shinya Fukuda, Mitsunori Itoh, Takashi Noda, Takeshi J Biol Chem Research Article Both the biogenesis and functions of osteoclasts and macrophages involves dynamic membrane traffic. We screened transcript levels for Rab family small GTPases related to osteoclasts and identified Rab38. Rab38 expression is upregulated during osteoclast differentiation and maturation. In osteoclasts, both Rab38 and its paralog, Rab32, colocalize to lysosome-related organelles (LROs). In macrophages, Rab32 is also found in LROs. LROs are part of the endocytic pathway but are distinct from lysosomes. After receptor activator of NF-κB ligand stimulation, LROs contain cathepsin K and tartrate-resistant acid phosphatase inside and help both proteins to accumulate around bone resorption pits. After osteoclast maturation, these enzymes are hardly found within LROs. In macrophages derived from Rab32 and Rab38 double knockout mice, both acidification and V-ATPase a3 localization were severely compromised. Both the double knockout macrophage and bafilomycin-treated wildtype macrophage show an increase in Lamp1-positive organelles, implying that biogenesis of lysosomes and LROs are related. These results indicate that Rab32 and Rab38 both play a crucial role in LRO biogenesis in macrophages and in osteoclasts. American Society for Biochemistry and Molecular Biology 2023-08-23 /pmc/articles/PMC10518718/ /pubmed/37625588 http://dx.doi.org/10.1016/j.jbc.2023.105191 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Noda, Kazuya
Lu, Shiou-Ling
Chen, Siyu
Tokuda, Kanako
Li, Yangjie
Hao, Feike
Wada, Yoh
Sun-Wada, Ge-Hong
Murakami, Shinya
Fukuda, Mitsunori
Itoh, Takashi
Noda, Takeshi
Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages
title Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages
title_full Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages
title_fullStr Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages
title_full_unstemmed Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages
title_short Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages
title_sort characterization of rab32- and rab38-positive lysosome-related organelles in osteoclasts and macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518718/
https://www.ncbi.nlm.nih.gov/pubmed/37625588
http://dx.doi.org/10.1016/j.jbc.2023.105191
work_keys_str_mv AT nodakazuya characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT lushiouling characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT chensiyu characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT tokudakanako characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT liyangjie characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT haofeike characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT wadayoh characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT sunwadagehong characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT murakamishinya characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT fukudamitsunori characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT itohtakashi characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages
AT nodatakeshi characterizationofrab32andrab38positivelysosomerelatedorganellesinosteoclastsandmacrophages