Trafficking-defective mutant PROKR2 cycles between endoplasmic reticulum and Golgi to attenuate endoplasmic reticulum stress

Abstract

Significance The endoplasmic reticulum (ER) possesses a quality control system that prevents misfolded proteins from leaving the ER for routing to the ER-associated degradation pathway. Some misfolded proteins can escape the ER to reach the Golgi, where they are then retrieved from the Golgi back to the ER for degradation, but why this occurs needs to be clarified. Studying a mutant prokineticin receptor 2 identified in patients with hypogonadotropic hypogonadism as a model, we find that the post-ER retrieval system provides another layer of quality control and also lowers the load of misfolded proteins in the ER to reduce ER stress. Our findings reveal the importance of a post-ER quality control mechanism in contributing to cellular homeostasis.