Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation in<i>Caenorhabditis elegans</i>

Sasaki, A; Nakae, Isei; Nagasawa, Maya; Hashimoto, Keisuke; Abe, Fumiko; Saito, Kota; Fukuyama, Masamitsu; Gengyo-Ando, Keiko; Mitani, Shohei; Katada, Toshiaki; Kontani, Kenji

doi:10.1091/mbc.e12-08-0628

Cited by 42 publications

(39 citation statements)

References 45 publications

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“…Recent data has suggested that in metazoan cells, Arl8b directly binds to Vps41 and regulates assembly of the HOPS complex on lysosomal membranes. 23,25,46,47 Accordingly, Arl8b-depletion impaired lysosomal localization of Vps41 and other HOPS subunits. Furthermore, Arl8b-binding was required for Vps41 function in epidermal growth factor receptor (EGFR) trafficking to lysosomes and its lysosomal degradation.…”

Section: Arl8b Regulates Lysosomal Motility Through Interaction With mentioning

confidence: 96%

“…23 A similar function for Arl8 was also discerned in Caenorhabditis elegans, where Arl8 was identified as a novel factor required for delivery of phagocytosed cargo to lysosomes. 25 Loss of Arl8 gene in C. elegans resulted in the delayed degradation and subsequent accumulation of apoptotic germ cells due to a defect in the formation of the phago-lysosomal compartment. Consistent with the previous reports in mammalian cells, the Arl8-binding to Vps41 was also found to be conserved in C. elegans.…”

Section: Arl8b Regulates Phagosome-lysosome Fusion and Microbial Pathmentioning

confidence: 99%

“…Consistent with the previous reports in mammalian cells, the Arl8-binding to Vps41 was also found to be conserved in C. elegans. 25 Many pathogenic microorganisms that invade eukaryotic cells exploit the host cell machinery for their survival. One such facultative intracellular pathogen, Salmonella enterica serovar typhimurium, establishes a replicative niche in host cells called the Salmonella-containing vacuole (SCV), through a process that involves extensive modulation of the host endocytic machinery.…”

Section: Arl8b Regulates Phagosome-lysosome Fusion and Microbial Pathmentioning

confidence: 99%

“…20 Arl8 is emerging as an important regulator of lysosome motility and membrane trafficking in several organisms. [20][21][22][23][24][25] In this review, we provide the first comprehensive overview of the known functions of the Arl8 family, particularly Arl8b, and highlight the interaction of Arl8b with effector proteins and its function in regulating the biology of the lysosome.…”

Section: Introductionmentioning

confidence: 99%

“…20,24 Arl8 localization as well as its function in regulating lysosome positioning and trafficking has since been found to be conserved across evolution. 23,25,33,34 Arl8 is distinct from the other Arf proteins (but similar to the Arls) in that it lacks a conserved glycine residue at the second position crucial for myristoylation-a post-translational lipid modification required for membrane targeting of all Arf proteins. 11 The glycine residue is replaced by leucine in case of Arl8b, and by isoleucine in case of Arl8a, rendering the human Arl8 proteins as potential substrates for N-acetyl transferase complex C (NatC).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology

Khatter¹,

Sindhwani

Sharma³

2015

Cellular Logistics

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Section: Arl8b Regulates Lysosomal Motility Through Interaction With mentioning

confidence: 96%

Section: Arl8b Regulates Phagosome-lysosome Fusion and Microbial Pathmentioning

confidence: 99%

Section: Arl8b Regulates Phagosome-lysosome Fusion and Microbial Pathmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology

Khatter¹,

Sindhwani

Sharma³

2015

Cellular Logistics

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The Arf family GTPases: Regulation of vesicle biogenesis and beyond

Guan

2023

BioEssays

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The Arf family proteins are best known for their roles in the vesicle biogenesis. However, they also play fundamental roles in a wide range of cellular regulation besides vesicular trafficking, such as modulation of lipid metabolic enzymes, cytoskeleton remodeling, ciliogenesis, lysosomal, and mitochondrial morphology and functions. Growing studies continue to expand the downstream effector landscape of Arf proteins, especially for the less‐studied members, revealing new biological functions, such as amino acid sensing. Experiments with cutting‐edge technologies and in vivo functional studies in the last decade help to provide a more comprehensive view of Arf family functions. In this review, we summarize the cellular functions that are regulated by at least two different Arf members with an emphasis on those beyond vesicle biogenesis.

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Juvenile mucopolysaccharidosis plus disease caused by a missense mutation in VPS33A

et al. 2022

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A rare and fatal disease resembling mucopolysaccharidosis in infants, is caused by impaired intracellular endocytic trafficking due to deficiency of core components of the intracellular membrane-tethering protein complexes, HOPS, and CORVET. Whole exome sequencing identified a novel VPS33A mutation in a patient suffering from a variant form of mucopolysaccharidosis. Electron and confocal microscopy, immunoblotting, and glycosphingolipid trafficking experiments were undertaken to investigate the effects of the mutant VPS33A in patient-derived skin fibroblasts. We describe an attenuated juvenile form of VPS33A-related syndrome-mucopolysaccharidosis plus in a man who is homozygous for a hitherto unknown missense mutation (NM_022916.4: c.599 G>C; NP_075067.2:p. Arg200Pro) in a conserved region of the VPS33A gene.Urinary glycosaminoglycan (GAG) analysis revealed increased heparan, dermatan sulphates, and hyaluronic acid. We showed decreased abundance of VPS33A in patient derived fibroblasts and provided evidence that the p.Arg200Pro mutation leads to destablization of the protein and proteasomal degradation. As in the infantile form of mucopolysaccharidosis plus, the endocytic compartment in the fibroblasts also expanded-a phenomenon accompanied by increased endolysosomal acidification and impaired intracellular glycosphingolipid trafficking. Experimental treatment of the patient's cultured fibroblasts with the proteasome inhibitor, bortezomib, or exposure to an inhibitor of glucosylceramide synthesis, eliglustat, improved glycosphingolipid trafficking. To our knowledge this is the first report of an attenuated juvenile form of VPS33A insufficiency characterized by appreciable residual endosomal-lysosomal trafficking and a milder mucopolysaccharidosis plus than the disease in infants. Our findings expand the proof of concept of redeploying clinically approved drugs for

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Arl8/ARL-8 functions in apoptotic cell removal by mediating phagolysosome formation inCaenorhabditis elegans

Cited by 42 publications

References 45 publications

Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology

Arf-like GTPase Arl8: Moving from the periphery to the center of lysosomal biology

The Arf family GTPases: Regulation of vesicle biogenesis and beyond

Juvenile mucopolysaccharidosis plus disease caused by a missense mutation in VPS33A

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