The K/HDEL receptor does not recycle but instead acts as a Golgi-gatekeeper

Author(s):Show less -

Alvim, Jonas C. ; Bolt, Robert M. ; An, Jing ; Kamisugi, Yasuko ; Cuming, Andrew ; Silva-Alvim, Fernanda A. L. ; Concha, Juan O. ; da Silva, Luis L. P. ; Hu, Meiyi ; Hirsz, Dominique ; Denecke, Jurgen

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 14, n. 1, p. 16-pg., 2023-03-23.

Abstract

Accurately measuring the ability of the K/HDEL receptor (ERD2) to retain the ER cargo Amy-HDEL has questioned earlier results on which the popular receptor recycling model is based upon. Here we demonstrate that ERD2 Golgi-retention, rather than fast ER export supports its function. Ligand-induced ERD2 redistribution is only observed when the C-terminus is masked or mutated, compromising the signal that prevents Golgi-to-ER transport of the receptor. Forcing COPI mediated retrograde transport destroys receptor function, but introducing ER-to-Golgi export or cis-Golgi retention signals re-activate ERD2 when its endogenous Golgi-retention signal is masked or deleted. We propose that ERD2 remains fixed as a Golgi gatekeeper, capturing K/HDEL proteins when they arrive and releasing them again into a subdomain for retrograde transport back to the ER. An in vivo ligand:receptor ratio far greater than 100 to 1 strongly supports this model, and the underlying mechanism appears to be extremely conserved across kingdoms. In contrast to the current model based on fast recycling of the K/HDEL receptor (ERD2) between the ER and the Golgi apparatus, here authors show evidence that ERD2 is specifically retained in the Golgi apparatus and evades joining its ligands en route to the ER. (AU)

• FAPESP's process: 20/11900-6 - Study of the mechanism of Orthobunyavirus intracelular transport and externalization
• Grantee: Juan Oswaldo Concha Casaverde
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/26119-0 - Emerging and re-emerging viruses: biology, pathogenesis and prospection
• Grantee: Eurico de Arruda Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/02418-9 - Molecular mechanisms of Oropouche Virus assembly
• Grantee: Luis Lamberti Pinto da Silva
• Support Opportunities: Regular Research Grants