{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:46:01Z","timestamp":1779889561481,"version":"3.53.1"},"reference-count":69,"publisher":"American Society for Cell Biology (ASCB)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>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\u2013lysosome 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.<\/jats:p>","DOI":"10.1091\/mbc.e25-08-0412","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:02:56Z","timestamp":1775149376000},"source":"Crossref","is-referenced-by-count":1,"title":["RANKL-inducible Arl8b effector RUFY4 drives HOPS-mediated lysosomal maturation and trafficking in osteoclasts"],"prefix":"10.1091","volume":"37","author":[{"given":"Kshitiz","family":"Walia","sequence":"first","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash B.","family":"Arya","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Chouhan","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshdeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medha","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5476-4127","authenticated-orcid":false,"given":"Amit","family":"Tuli","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"e_1_3_6_2_1","doi-asserted-by":"publisher","DOI":"10.2350\/10-09-0909-CR.1"},{"key":"e_1_3_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000727"},{"key":"e_1_3_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.03.221"},{"key":"e_1_3_6_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.6.1863"},{"key":"e_1_3_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2999"},{"key":"e_1_3_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2885"},{"key":"e_1_3_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1928"},{"key":"e_1_3_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1990.tb02999.x"},{"key":"e_1_3_6_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00779"},{"key":"e_1_3_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5127"},{"key":"e_1_3_6_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.063032"},{"key":"e_1_3_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmrpl\/ziae034"},{"key":"e_1_3_6_14_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00082"},{"key":"e_1_3_6_15_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.071107"},{"key":"e_1_3_6_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8832"},{"key":"e_1_3_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116538"},{"key":"e_1_3_6_18_1","doi-asserted-by":"publisher","DOI":"10.4248\/BR201301003"},{"key":"e_1_3_6_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.86330"},{"key":"e_1_3_6_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.51.34120"},{"key":"e_1_3_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.06.009"},{"key":"e_1_3_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.06.015"},{"key":"e_1_3_6_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02958"},{"key":"e_1_3_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.29168"},{"key":"e_1_3_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08238"},{"key":"e_1_3_6_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000003115"},{"key":"e_1_3_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28952-y"},{"key":"e_1_3_6_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.162651"},{"key":"e_1_3_6_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/21592799.2015.1086501"},{"key":"e_1_3_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-024-00326-8"},{"key":"e_1_3_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.033"},{"key":"e_1_3_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2204"},{"key":"e_1_3_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29077-y"},{"key":"e_1_3_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650040605"},{"key":"e_1_3_6_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19103004"},{"key":"e_1_3_6_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.8.8954"},{"key":"e_1_3_6_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc7209"},{"key":"e_1_3_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108973"},{"key":"e_1_3_6_39_1","first-page":"115","article-title":"Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis","volume":"21","author":"Manolagas SC","year":"2000","unstructured":"Manolagas SC (2000). Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21, 115\u2013137.","journal-title":"Endocr Rev"},{"key":"e_1_3_6_40_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201607085"},{"key":"e_1_3_6_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700829"},{"key":"e_1_3_6_42_1","doi-asserted-by":"publisher","DOI":"10.7205\/MILMED-D-16-00234"},{"key":"e_1_3_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2012.08.030"},{"key":"e_1_3_6_44_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.200519"},{"key":"e_1_3_6_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.15.1767"},{"key":"e_1_3_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-65568-4"},{"key":"e_1_3_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.12.5253-5269.2005"},{"key":"e_1_3_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168293"},{"key":"e_1_3_6_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.041087"},{"key":"e_1_3_6_50_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202108001"},{"key":"e_1_3_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.10.007"},{"key":"e_1_3_6_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207655"},{"key":"e_1_3_6_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46826-3_32"},{"key":"e_1_3_6_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13211766"},{"key":"e_1_3_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2021.06.003"},{"key":"e_1_3_6_56_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80901"},{"key":"e_1_3_6_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2076"},{"key":"e_1_3_6_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-5"},{"key":"e_1_3_6_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1504"},{"key":"e_1_3_6_60_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201501059"},{"key":"e_1_3_6_61_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-05-0259"},{"key":"e_1_3_6_62_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.3.377"},{"key":"e_1_3_6_63_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.202333"},{"key":"e_1_3_6_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30328"},{"key":"e_1_3_6_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46417-2"},{"issue":"1","key":"e_1_3_6_66_1","first-page":"45","article-title":"FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption","volume":"14","author":"Wang L","year":"2025","unstructured":"Wang L, Minocha T, Das BK, Kunika MD, Kannan A, Gao L, Mohan S, Xing W, Varughese KI, Zhao H (2025). FAM98 Family Proteins Play Distinct Roles in Osteoclastogenesis and Bone Resorption. Biology (Basel) 14(1), 45. https:\/\/doi.org\/10.3390\/biology14010045.","journal-title":"Biology (Basel)"},{"key":"e_1_3_6_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005057"},{"key":"e_1_3_6_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027285"},{"key":"e_1_3_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00326-1"},{"key":"e_1_3_6_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010999200"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:13:12Z","timestamp":1777399992000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.E25-08-0412"}},"subtitle":[],"editor":[{"given":"Sergio","family":"Grinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":69,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"alternative-id":["10.1091\/mbc.E25-08-0412"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e25-08-0412","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"article-number":"ar43"}}