The homotypic fusion and protein sorting (HOPS) complex is a multi-subunit complex conserved from yeast to mammals that regulates late endosome and lysosome fusion. However, little is known about how the HOPS complex is recruited to lysosomes in mammalian cells. Here, we report that the small GTPase Arl8b, but not Rab7 (also known as RAB7A), is essential for membrane localization of the human (h)Vps41 subunit of the HOPS complex. Assembly of the core HOPS subunits to Arl8b- and hVps41-positive lysosomes is guided by their subunit-subunit interactions. RNA interference (RNAi)-mediated depletion of hVps41 resulted in the impaired degradation of EGFR that was rescued upon expression of wild-type but not an Arl8b-binding-defective mutant of hVps41, suggesting that Arl8b-dependent lysosomal localization of hVps41 is required for its endocytic function. Furthermore, we have also identified that the Arl8b effector SKIP (also known as PLEKHM2) interacts with and recruits HOPS subunits to Arl8b and kinesin-positive peripheral lysosomes. Accordingly, RNAi-mediated depletion of SKIP impaired lysosomal trafficking and degradation of EGFR. These findings reveal that Arl8b regulates the association of the human HOPS complex with lysosomal membranes, which is crucial for the function of this tethering complex in endocytic degradation.
机构:
Osaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Aoyama, Minako
Sun-Wada, Ge-Hong
论文数: 0引用数: 0
h-index: 0
机构:
Doshisha Womens Coll Liberal Arts, Fac Pharmaceut Sci, Kyoto 6100395, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Sun-Wada, Ge-Hong
Yamamoto, Akitsugu
论文数: 0引用数: 0
h-index: 0
机构:
Nagahama Inst Biosci & Technol, Dept Cell Biol, Nagahama, Shiga 5260829, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Yamamoto, Akitsugu
Yamamoto, Masamichi
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Univ, Dev Genet Grp, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan
Japan Sci & Technol Agcy, Chiyoda Ku, Tokyo 1020076, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Yamamoto, Masamichi
Hamada, Hiroshi
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Univ, Dev Genet Grp, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan
Japan Sci & Technol Agcy, Chiyoda Ku, Tokyo 1020076, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Hamada, Hiroshi
Wada, Yoh
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
机构:
Aix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, FranceAix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France
Capo, Christian
论文数: 引用数:
h-index:
机构:
Bonatti, Stefano
Nebreda, Angel
论文数: 0引用数: 0
h-index: 0
机构:
Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
ICREA, Barcelona 08028, SpainAix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France
Nebreda, Angel
Toman, Rudolf
论文数: 0引用数: 0
h-index: 0
机构:
Slovak Acad Sci, Inst Virol, Lab Diag & Prevent Rickettsial & Chlamydial Infec, Bratislava 84505, SlovakiaAix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Delahaye, Jared L.
Foster, Olivia K.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Foster, Olivia K.
Vine, Annalise
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Vine, Annalise
Saxton, Daniel S.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Saxton, Daniel S.
Curtin, Thomas P.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Curtin, Thomas P.
Somhegyi, Hannah
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Somhegyi, Hannah
Salesky, Rebecca
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Salesky, Rebecca
Hermann, Greg J.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
机构:
Harvard Div Med Sci, Grad Program Immunol, Boston, MA 02115 USA
Harvard MIT MD PhD Program, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Garg, Salil
Sharma, Mahak
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Sharma, Mahak
Ung, Cindy
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Ung, Cindy
Tuli, Amit
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Tuli, Amit
Barral, Duarte C.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Barral, Duarte C.
Hava, David L.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Hava, David L.
Veerapen, Natacha
论文数: 0引用数: 0
h-index: 0
机构:
Univ Birmingham, Sch Biosci, Birmingham, W Midlands, EnglandBrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Veerapen, Natacha
Besra, Gurdyal S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Birmingham, Sch Biosci, Birmingham, W Midlands, EnglandBrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Besra, Gurdyal S.
Hacohen, Nir
论文数: 0引用数: 0
h-index: 0
机构:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Hacohen, Nir
Brenner, Michael B.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
机构:
Osaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Aoyama, Minako
Sun-Wada, Ge-Hong
论文数: 0引用数: 0
h-index: 0
机构:
Doshisha Womens Coll Liberal Arts, Fac Pharmaceut Sci, Kyoto 6100395, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Sun-Wada, Ge-Hong
Yamamoto, Akitsugu
论文数: 0引用数: 0
h-index: 0
机构:
Nagahama Inst Biosci & Technol, Dept Cell Biol, Nagahama, Shiga 5260829, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Yamamoto, Akitsugu
Yamamoto, Masamichi
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Univ, Dev Genet Grp, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan
Japan Sci & Technol Agcy, Chiyoda Ku, Tokyo 1020076, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Yamamoto, Masamichi
Hamada, Hiroshi
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Univ, Dev Genet Grp, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan
Japan Sci & Technol Agcy, Chiyoda Ku, Tokyo 1020076, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
Hamada, Hiroshi
Wada, Yoh
论文数: 0引用数: 0
h-index: 0
机构:
Osaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, JapanOsaka Univ, Div Biol Sci, Inst Sci & Ind Res, Osaka 5670047, Japan
机构:
Aix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, FranceAix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France
Capo, Christian
论文数: 引用数:
h-index:
机构:
Bonatti, Stefano
Nebreda, Angel
论文数: 0引用数: 0
h-index: 0
机构:
Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
ICREA, Barcelona 08028, SpainAix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France
Nebreda, Angel
Toman, Rudolf
论文数: 0引用数: 0
h-index: 0
机构:
Slovak Acad Sci, Inst Virol, Lab Diag & Prevent Rickettsial & Chlamydial Infec, Bratislava 84505, SlovakiaAix Marseille Univ, INSERM U1095, IRD198, CNRS UMR 7278, F-13385 Marseille 05, France
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Delahaye, Jared L.
Foster, Olivia K.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Foster, Olivia K.
Vine, Annalise
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Vine, Annalise
Saxton, Daniel S.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Saxton, Daniel S.
Curtin, Thomas P.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Curtin, Thomas P.
Somhegyi, Hannah
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Somhegyi, Hannah
Salesky, Rebecca
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Salesky, Rebecca
Hermann, Greg J.
论文数: 0引用数: 0
h-index: 0
机构:
Lewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
Lewis & Clark Coll, Program Biochem & Mol Biol, Portland, OR 97219 USALewis & Clark Coll, Dept Biol, Portland, OR 97219 USA
机构:
Harvard Div Med Sci, Grad Program Immunol, Boston, MA 02115 USA
Harvard MIT MD PhD Program, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Garg, Salil
Sharma, Mahak
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Sharma, Mahak
Ung, Cindy
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Ung, Cindy
Tuli, Amit
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Tuli, Amit
Barral, Duarte C.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Barral, Duarte C.
Hava, David L.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Hava, David L.
Veerapen, Natacha
论文数: 0引用数: 0
h-index: 0
机构:
Univ Birmingham, Sch Biosci, Birmingham, W Midlands, EnglandBrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Veerapen, Natacha
Besra, Gurdyal S.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Birmingham, Sch Biosci, Birmingham, W Midlands, EnglandBrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Besra, Gurdyal S.
Hacohen, Nir
论文数: 0引用数: 0
h-index: 0
机构:
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
Hacohen, Nir
Brenner, Michael B.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USABrigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA