Evidence map›Paper›PMID 25908847›Full record

ArticleJournal of cell science2015

The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes.

Divya Khatter, Vivek B Raina, Devashish Dwivedi, Aastha Sindhwani, Surbhi Bahl, Mahak Sharma

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.

  1. Guideline
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  5. NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025
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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Divya KhatterDepartment of Biological Sciences, Indian Institute of Science Education and Research-Mohali (IISERM), India.
Vivek B RainaDepartment of Biological Sciences, Indian Institute of Science Education and Research-Mohali (IISERM), India.
Devashish DwivediDepartment of Biological Sciences, Indian Institute of Science Education and Research-Mohali (IISERM), India.
Aastha SindhwaniDepartment of Biological Sciences, Indian Institute of Science Education and Research-Mohali (IISERM), India.
Surbhi BahlDepartment of Biological Sciences, Indian Institute of Science Education and Research-Mohali (IISERM), India.
Mahak SharmaDepartment of Biological Sciences, Indian Institute of Science Education and Research-Mohali (IISERM), India msharma@iisermohali.ac.in.
Indian Institute of Science Education and Research Mohali · INWellcome Trust/DBT India Alliance · IN

Funding

DBT-Wellcome Trust India Alliance IA/I/12/1/500523Wellcome TrustWellcome Trust IA/I/12/500523
6 · The paper itself

Abstract

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.

Indexed as

Adaptor Proteins, Signal TransducingADP-Ribosylation FactorsAnimalsAutophagy-Related ProteinsCell MembraneEndocytosisErbB ReceptorsGuanosine TriphosphateHeLa CellsHumansIntracellular Signaling Peptides and ProteinsLysosomesMammalsMultiprotein ComplexesPolymorphism, Single NucleotideProtein BindingAdaptor Proteins, Signal TransducingADP-Ribosylation FactorsARL8B protein, humanAutophagy-Related ProteinsErbB ReceptorsGuanosine TriphosphateIntracellular Signaling Peptides and ProteinsMultiprotein ComplexesProtein SubunitsSPHKAP protein, humanVesicular Transport ProteinsVPS39 protein, humanVPS41 protein, humanArl8bhVps41LysosomeMammalian HOPS complexSKIP

Identifiers

PMID25908847
PMCPMC4432227
OpenAlexW2130324836

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.