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primary topic: RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts

RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts
type: AcademicArticle
type: Article
abstract: Osteoclast-mediated bone resorption depends on the secretion of lysosomal hydrolases via the fusion of secretory lysosomes with the ruffled border, yet the molecular mechanisms governing lysosomal trafficking and fusion remain incompletely understood. Here, we demonstrate that the small GTPase Arl8b regulates the processing of osteoclastspecific lysosomal hydrolase, cathepsin K, and the positioning of secretory lysosomes toward the actin ring. Accordingly, depletion of Arl8b led to defects in lysosome-mediated bone resorption in osteoclasts. We identify RUFY4 as a RANKL-inducible Arl8b effector that promotes lysosome clustering and maturation by linking Arl8b to Rab7 through the adaptor PLEKHM1 and recruiting the multi-subunit tethering factor HOPS complex to drive late endosome-lysosome fusion. Depletion of RUFY4 or HOPS subunits impairs cathepsin K processing and disrupts lysosome positioning, leading to reduced bone resorption activity. These findings suggest that Arl8b and its interaction partners play essential roles in biogenesis and positioning of secretory lysosomes, essential for osteoclast function in bone remodeling.
date: 2026-05-01
volume: 37
issue: 5
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
has document: RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts (HTML)
subject: QR Microbiology

RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts (HTML)
type: Document
has file: references (4).bib
has part: references (4).bib

AMER SOC CELL BIOLOGY
type: Organization

MOLECULAR BIOLOGY OF THE CELL
type: Collection

Priya Chouhan
type: Person
given name: Priya
family name: Chouhan

Subhash B. Arya
type: Person
given name: Subhash B.
family name: Arya

Kshitiz Walia
type: Person
given name: Kshitiz
family name: Walia

Amit Tuli
type: Person
given name: Amit
family name: Tuli

Medha Gupta
type: Person
given name: Medha
family name: Gupta

Arshdeep Kaur
type: Person
given name: Arshdeep
family name: Kaur

Gaurav Kumar
type: Person
given name: Gaurav
family name: Kumar

HTML Summary of #3453 RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts
format: text/html
primary topic: RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts

QR Microbiology
type: Concept