creators_name: Rawat, Shalini
creators_name: Chatterjee, Dhruba
creators_name: Marwaha, Rituraj
creators_name: Charak, Gitanjali
creators_name: Kumar, Gaurav
creators_name: Shaw, Shrestha
creators_name: Khatter, Divya
creators_name: Sharma, Sheetal
creators_name: Heus, Cecilia De
creators_name: Liv, Nalan
creators_name: Judith , Klumperman
creators_name: Tuli, Amit
creators_name: Sharma, Mahak
type: article
datestamp: 2024-07-15 03:52:47
lastmod: 2024-07-15 03:52:47
metadata_visibility: show
title: RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes
ispublished: pub
subjects: QR
note: The copyright of this article belongs to ROCKFELLER UNIVERSITY PRESS
abstract: Arl8b, an Arf-like GTP-binding protein, regulates cargo trafficking and positioning of lysosomes. However, it is unknown whether Arl8b regulates lysosomal cargo sorting. Here, we report that Arl8b binds to the Rab4 and Rab14 interaction partner, RUN and FYVE domain-containing protein (RUFY) 1, a known regulator of cargo sorting from recycling endosomes. Arl8b determines RUFY1 endosomal localization through regulating its interaction with Rab14. RUFY1 depletion led to a delay in CI-M6PR retrieval from endosomes to the TGN, resulting in impaired delivery of newly synthesized hydrolases to lysosomes. We identified the dynein-dynactin complex as an RUFY1 interaction partner, and similar to a subset of activating dynein adaptors, the coiled-coil region of RUFY1 was required for interaction with dynein and the ability to mediate dynein-dependent organelle clustering. Our findings suggest that Arl8b and RUFY1 play a novel role on recycling endosomes, from where this machinery regulates endosomes to TGN retrieval of CI-M6PR and, consequently, lysosomal cargo sorting.


date: 2022-10-25
date_type: published
publication: Journal of Cell Biology 
volume: 222
number: 1
publisher: ROCKFELLER UNIVERSITY PRESS
id_number: https://doi.org/10.1083/jcb.202108001
refereed: TRUE
official_url: https://rupress.org/jcb/article/222/1/e202108001/213572/RUFY1-binds-Arl8b-and-mediates-endosome-to-TGN-CI
citation:   Rawat, Shalini and Chatterjee, Dhruba and Marwaha, Rituraj and Charak, Gitanjali and Kumar, Gaurav and Shaw, Shrestha and Khatter, Divya and Sharma, Sheetal and Heus, Cecilia De and Liv, Nalan and Judith , Klumperman and Tuli, Amit and Sharma, Mahak  (2022) RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes.  Journal of Cell Biology , 222 (1).