Unknown

Dataset Information

0

Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway.


ABSTRACT: N?-lysine acetylation in the ER is an essential component of the quality control machinery. ER acetylation is ensured by a membrane transporter, AT-1/SLC33A1, which translocates cytosolic acetyl-CoA into the ER lumen, and two acetyltransferases, ATase1 and ATase2, which acetylate nascent polypeptides within the ER lumen. Dysfunctional AT-1, as caused by gene mutation or duplication events, results in severe disease phenotypes. Here, we used two models of AT-1 dysregulation to investigate dynamics of the secretory pathway: AT-1 sTg, a model of systemic AT-1 overexpression, and AT-1S113R/+, a model of AT-1 haploinsufficiency. The animals displayed reorganization of the ER, ERGIC, and Golgi apparatus. In particular, AT-1 sTg animals displayed a marked delay in Golgi-to-plasma membrane protein trafficking, significant alterations in Golgi-based N-glycan modification, and a marked expansion of the lysosomal network. Collectively our results indicate that AT-1 is essential to maintain proper organization and engagement of the secretory pathway.

SUBMITTER: Dieterich IA 

PROVIDER: S-EPMC7820588 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway.

Dieterich Inca A IA   Cui Yusi Y   Braun Megan M MM   Lawton Alexis J AJ   Robinson Nicklaus H NH   Peotter Jennifer L JL   Yu Qing Q   Casler Jason C JC   Glick Benjamin S BS   Audhya Anjon A   Denu John M JM   Li Lingjun L   Puglielli Luigi L  

Scientific reports 20210121 1


Nε-lysine acetylation in the ER is an essential component of the quality control machinery. ER acetylation is ensured by a membrane transporter, AT-1/SLC33A1, which translocates cytosolic acetyl-CoA into the ER lumen, and two acetyltransferases, ATase1 and ATase2, which acetylate nascent polypeptides within the ER lumen. Dysfunctional AT-1, as caused by gene mutation or duplication events, results in severe disease phenotypes. Here, we used two models of AT-1 dysregulation to investigate dynamic  ...[more]

Similar Datasets

2021-09-09 | PXD019770 | Pride
| S-EPMC6718414 | biostudies-literature
2019-08-05 | PXD013736 | Pride
| S-EPMC6440987 | biostudies-literature
| S-EPMC4489017 | biostudies-literature
| S-EPMC5505514 | biostudies-literature
| S-EPMC10594767 | biostudies-literature
| S-EPMC2911049 | biostudies-literature
| S-EPMC6363758 | biostudies-literature
2014-11-04 | GSE59814 | GEO