RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes

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).

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Official URL: https://rupress.org/jcb/article/222/1/e202108001/2...

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.

Item Type: Article
Additional Information: The copyright of this article belongs to ROCKFELLER UNIVERSITY PRESS
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 15 Jul 2024 03:52
Last Modified: 15 Jul 2024 03:52
URI: http://crdd.osdd.net/open/id/eprint/3150

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