scholarly journals Physiological importance of NGLY1, as revealed by rodent model analyses

2021 ◽  
Author(s):  
Haruhiko Fujihira ◽  
Makoto Asahina ◽  
Tadashi Suzuki
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Control System ◽  
Animal Models ◽  
Rodent Model ◽  
Rodent Models ◽  
Future Perspectives ◽  
Physiological Functions ◽  
Physiological Importance ◽  
Glycan Degradation

Summary Cytosolic peptide:N-glycanase (NGLY1) is an enzyme that cleaves N-glycans from glycoproteins that has been retrotranslocated from the endoplasmic reticulum (ER) lumen into the cytosol. It is known that NGLY1 is involved in the degradation of cytosolic glycans (non-lysosomal glycan degradation) as well as ER-associated degradation (ERAD), a quality control system for newly synthesized glycoproteins. The discovery of NGLY1 deficiency, which is caused by mutations in the human NGLY1 gene and results in multisystemic symptoms, has attracted interest in the physiological functions of NGLY1 in mammals. Studies using various animal models led to the identification of possible factors that contribute to the pathogenesis of NGLY1 deficiency. In this review, we summarize phenotypic consequences that have been reported for various Ngly1-deficient rodent models, and discuss future perspectives to provide more insights into the physiological functions of NGLY1.

scholarly journals Activation of Mammalian Unfolded Protein Response Is Compatible with the Quality Control System Operating in the Endoplasmic Reticulum

2004 ◽  
Vol 15 (6) ◽  
pp. 2537-2548 ◽  
Author(s):  
Satomi Nadanaka ◽  
Hiderou Yoshida ◽  
Fumi Kano ◽  
Masayuki Murata ◽  
Kazutoshi Mori
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Control System ◽  
Golgi Apparatus ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Unfolded Proteins ◽  
Unfolded Protein ◽  
Protein Response

Newly synthesized secretory and transmembrane proteins are folded and assembled in the endoplasmic reticulum (ER) where an efficient quality control system operates so that only correctly folded molecules are allowed to move along the secretory pathway. The productive folding process in the ER has been thought to be supported by the unfolded protein response (UPR), which is activated by the accumulation of unfolded proteins in the ER. However, a dilemma has emerged; activation of ATF6, a key regulator of mammalian UPR, requires intracellular transport from the ER to the Golgi apparatus. This suggests that unfolded proteins might be leaked from the ER together with ATF6 in response to ER stress, exhibiting proteotoxicity in the secretory pathway. We show here that ATF6 and correctly folded proteins are transported to the Golgi apparatus via the same route and by the same mechanism under conditions of ER stress, whereas unfolded proteins are retained in the ER. Thus, activation of the UPR is compatible with the quality control in the ER and the ER possesses a remarkable ability to select proteins to be transported in mammalian cells in marked contrast to yeast cells, which actively utilize intracellular traffic to deal with unfolded proteins accumulated in the ER.

Sign in / Sign up

Export Citation Format

Share Document