Proteomics

Dataset Information

0

Proinsulin dependent interaction between ENPL-1/GRP94 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.


ABSTRACT: Maturation of insulin is crucial for insulin secretion and function. ENPL[1]1/GRP94/HSP90B1 plays an important role in this process. ASNA-1/TRC40/GET3 and ENPL-1/GRP94 are conserved insulin secretion regulators in Caenorhabditis elegans and mammals and mouse mutants display type 2 diabetes. ENPL-1 and GRP94 bind proinsulin and regulate proinsulin levels in C. elegans and cultured cells. Here we found that ASNA-1 and ENPL-1 co-operated to regulate insulin secretion in worms via a physical interaction that required pro-DAF-28/insulin but occurred independently of the insulin binding site of ENPL-1. ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The interaction occurred in insulin expressing neurons and was sensitive to changes in pro-DAF-28 levels. The chaperone form of ASNA-1 is likely bound to ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed ASNA[1]1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 which is necessary to maintain proper insulin secretion in C. elegans and provides insights about how their loss might produce diabetes in mammals.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human) Caenorhabditis Elegans

TISSUE(S): Brain

SUBMITTER: Johannes Fuchs  

LAB HEAD: Gautam Kao

PROVIDER: PXD038504 | Pride | 2023-03-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
3048_UNIhuman_0miss_norm_ungrouped.msf Msf
3048_UNIhuman_0miss_norm_ungrouped.pdResult Other
3048_UNIhuman_0miss_norm_ungrouped_FDR1perc.xlsx Xlsx
Fusion_190211_21.raw Raw
Fusion_190211_22.raw Raw
Items per page:
1 - 5 of 24

Similar Datasets

2020-07-29 | GSE114160 | GEO
2017-03-09 | GSE85725 | GEO
2023-11-15 | GSE245844 | GEO
2023-11-15 | GSE245845 | GEO
2015-02-14 | E-GEOD-65929 | biostudies-arrayexpress
2024-09-16 | GSE226346 | GEO
2023-10-11 | GSE207498 | GEO
2012-12-03 | E-GEOD-39432 | biostudies-arrayexpress
2015-02-14 | GSE65929 | GEO
2010-05-16 | E-GEOD-18563 | biostudies-arrayexpress