PXD020562

PXD020562 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-24 07:33:34	ID requested
⏵ 1	2020-09-23 22:18:44	announced

Dataset with its publication pending

submitter keyword: Calreticulin, Calnexin, Alpha1-Antitrypsin, COPII, Secretory Trafficking

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

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PRIDE project URI

• PRIDE
  1. PXD020562
     1. Label: PRIDE project
     2. Name: Calreticulin enhances the secretory trafficking of a polymerogenic alpha1-antitrypsin