PXD020562 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Calreticulin enhances the secretory trafficking of a polymerogenic alpha1-antitrypsin |
Description | α-1-antitrypsin (AAT) regulates protease activity in the lungs and liver. The presence of one or more copies of a mutant Z allele (AAT (E342K), called ATZ), results in low serum levels of ATZ along with intracellular inclusions of polymeric forms, causing lung emphysema and liver cirrhosis. Our experiments show that calreticulin (CRT), an endoplasmic reticulum (ER) glycoprotein chaperone, promotes the secretory trafficking of ATZ, enhancing the media to cell ratio. This effect is more specific for ATZ compared with AAT, and is only partially dependent on the glycan-binding site of CRT. The CRT-related chaperone calnexin (CNX) does not promote enhanced ATZ secretory trafficking, despite the higher cellular abundance of CNX-ATZ complexes. CRT deficiency alters the distributions of ATZ-ER chaperone complexes, increasing ATZ-BiP binding and inclusion body (IB) formation, and reducing ATZ interactions with components required for ER-Golgi trafficking. These findings indicate a novel role for CRT in promoting the secretory trafficking of a polymerogenic protein. Inefficient secretory trafficking of ATZ in the absence of CRT is coincident with enhanced accumulation of ER-derived ATZ IBs. |
HostingRepository | PRIDE |
AnnounceDate | 2020-09-24 |
AnnouncementXML | Submission_2020-09-23_22:18:44.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Boning Yang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue; deamidated residue |
Instrument | Orbitrap Fusion; Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-07-24 07:33:34 | ID requested | |
⏵ 1 | 2020-09-23 22:18:44 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Calreticulin, Calnexin, Alpha1-Antitrypsin, COPII, Secretory Trafficking |
Contact List
Malini Raghavan |
contact affiliation | Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA |
contact email | malinir@umich.edu |
lab head | |
Boning Yang |
contact affiliation | University of Michigan |
contact email | boningya@umich.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020562
- Label: PRIDE project
- Name: Calreticulin enhances the secretory trafficking of a polymerogenic alpha1-antitrypsin