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primary topic: Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis

Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis
type: AcademicArticle
type: Article
abstract: The small GTP-binding protein Arl8b is established as a regulator of lysosome positioning and fusion, yet its role in lysosome biogenesis remains unclear. Here, we investigate the role of Arl8b in the trafficking of newly synthesized LAMP1 to lysosomes using the Retention Using Selective Hook (RUSH) assay. We find that Arl8b localizes to post-endocytic LAMP1-containing vesicles prior to fusion with acidic lysosomes. Arl8b depletion leads to Rab11a-dependent recycling of LAMP1 to the plasma membrane, impairing its lysosomal delivery. Mechanistically, Arl8b recruits the Rab11a GAP, TBC1D9B, to LAMP1-positive membranes, and TBC1D9B depletion similarly disrupts LAMP1 sorting. Notably, TBC1D9B knockdown also impairs the retrieval of cation-independent mannose-6-phosphate receptor (CI-M6PR) from Rab11a- and Rab14-positive endosomes to the trans-Golgi network, impairing pro-cathepsin trafficking and cargo degradation. These findings reveal that Arl8b-mediated recruitment of Rab GAP TBC1D9B is crucial for inactivation of the Rab11a recycling pathway, leading to efficient sorting of lysosomal cargo to their functional location.
date: 2026-07-06
volume: 225
issue: 7
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
has document: Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis (HTML)
subject: QR Microbiology

Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis (HTML)
type: Document
has file: references.bib
has part: references.bib

Rockefeller University Press
type: Organization

J. Cell Biol.
type: Collection

Medha Gupta
type: Person
given name: Medha
family name: Gupta

Mahak Sharma
type: Person
given name: Mahak
family name: Sharma

Amit Tuli
type: Person
given name: Amit
family name: Tuli

Yogita Phogat
type: Person
given name: Yogita
family name: Phogat

Sandeep Choubey
type: Person
given name: Sandeep
family name: Choubey

Kshitiz Walia
type: Person
given name: Kshitiz
family name: Walia

Priya Chouhan
type: Person
given name: Priya
family name: Chouhan

Saikat Debnath
type: Person
given name: Saikat
family name: Debnath

HTML Summary of #3480 Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis
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primary topic: Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis

QR Microbiology
type: Concept