@ARTICLE{Walia2026-jn,
  title     = "{RANKL-inducible} Arl8b effector {RUFY4} drives {HOPS-mediated}
               lysosomal maturation and trafficking in osteoclasts",
  author    = "Walia, Kshitiz and Kumar, Gaurav and Arya, Subhash B and
               Chouhan, Priya and Kaur, Arshdeep and Gupta, Medha and Tuli,
               Amit",
  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 osteoclast-specific 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.",
  journal   = "Mol. Biol. Cell",
  publisher = "American Society for Cell Biology (ASCB)",
  volume    =  37,
  number    =  5,
  pages     = "ar43",
  month     =  may,
  year      =  2026,
  language  = "en"
}
