SPELL - Nematode

Citation	Podraza-Farhanieh A, Raj D, Kao G, Naredi P. A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans. Development, 2023.
PubMed ID	36939052
Short Description	A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans. GEO Record: N.A. Platform: N.A. Download gene-centric, log2 transformed data: WBPaper00065132.ce.ms.csv
# of Conditions	8
Full Description	Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes. ENPL-1/GRP94 binds proinsulin and regulates proinsulin levels in C. elegans and mammalian cells. Here, we have found that ASNA-1 and ENPL-1 cooperate to regulate insulin secretion in worms via a physical interaction that is independent of the insulin-binding site of ENPL-1. The interaction occurs in DAF-28/insulin-expressing neurons and is sensitive to changes in DAF-28 pro-peptide levels. Consistently, ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The chaperone form of ASNA-1 was likely the interaction partner of ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization to the Golgi was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed the ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 that is necessary to maintain proper insulin secretion in C. elegans and provides insights into how their loss might cause diabetes in mammals. Experimental Details: MassSpec_WBPaper00065132:asna-1(ok938)_rep1 MassSpec_WBPaper00065132:asna-1(ok938)_rep2 MassSpec_WBPaper00065132:asna-1(ok938)_rep3and4 MassSpec_WBPaper00065132:asna-1(ok938)_rep5 MassSpec_WBPaper00065132:N2_rep1 MassSpec_WBPaper00065132:N2_rep2 MassSpec_WBPaper00065132:N2_rep3 MassSpec_WBPaper00065132:N2_rep4.
Tags	Method: proteomics, Species: Caenorhabditis elegans, Topic: WT vs. mutant