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Systemic Regulation of ER Proteostasis

内质网蛋白质稳态的系统调节

基本信息

批准号：
10625295
负责人：
Chung Yin Kimberly Tsui
金额：
$ 7.38万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10625295
关键词：
Aging Biological Assay CRISPR screen Caenorhabditis elegans Cell Communication Cell Culture Techniques Cell Line Cells Cellular Stress Chemistry Clustered Regularly Interspaced Short Palindromic Repeats Communication Cytoprotection Detection Disease Distal Endoplasmic Reticulum Enzymes GRP78 gene Genes Glycoproteins Health Homeostasis Human Induced pluripotent stem cell derived neurons Intestines Ischemia Knock-out Label Longevity Mediating Methods Microscopy Modeling Mus Neurons Organism Pathway interactions Phosphines Physiological Protein Glycosylation Proteins Proteome Quality Control Regulation Reperfusion Injury Reporter Resistance Role Signal Pathway Signal Transduction Signaling Molecule Stress Supplementation Techniques Testing Tissues Toxic effect Tunicamycin Up-Regulation Work biological adaptation to stress endoplasmic reticulum stress experience experimental study extracellular genome-wide glycosylation hepatoma cell improved in vivo induced pluripotent stem cell insight liquid chromatography mass spectrometry nerve stem cell novel novel strategies pharmacologic promoter protein folding protein metabolite protein misfolding proteostasis proteotoxicity response stressor sugar unpublished works

项目摘要

Abstract Proper activation of cellular stress response pathways allows cells to adapt and maintain homeostasis during stressful conditions. While these pathways are typically thought to be regulated within a cell, recent studies in mice and C. elegans suggest that cellular stress experience in certain cells can distally activate stress response in other tissues. For example, work from our lab have shown that neuronal activation of the endoplasmic reticulum Unfolded Protein Response (UPRER) induces UPRER in the intestine of C. elegans, promoting stress resistance and longevity. These findings clearly demonstrates the importance of systemic regulation of ER proteostasis in organismal health. However, the mechanisms and the signaling molecules underlying such inter-tissue regulation of ER proteostasis remain unknown. Our preliminary work has identified N-acetylglucosamine (GlcNAc), an essential metabolite for protein glycosylation, as a candidate signaling molecule for regulating ER proteostasis across cells. I propose to elucidate mechanisms by which GlcNAc is released by stressed cells and utilized by recipient cells, and to develop novel methods to examine in vivo tissue-to-tissue GlcNAc signaling using neuronal cell culture and C. elegans models. This work will uncover how GlcNAc regulates systemic ER proteostasis, and establish novel techniques to study how sugars and protein glycosylation mediate cell-cell communication.

摘要