PXD023091-1

PXD023091 is an original dataset announced via ProteomeXchange.

Title	Glycosylation Limits Forward Trafficking of the Tetraspan Membrane Protein PMP22
Description	Peripheral myelin protein 22 (PMP22) is a tetraspan integral membrane protein for which mistrafficking-causing mutations are linked to the inherited peripheral neuropathy, Charcot-Marie-Tooth disease (CMTD). Wild type (WT) PMP22 is an inefficient folder with ~20% of the protein trafficking to the plasma membrane. We discovered that N-linked glycosylation significantly limits forward trafficking of WT and disease variants of PMP22. N-glycosylation of WT PMP22 was found to occur primarily post-translationally. Glycosylation inhibition dramatically increased PMP22 trafficking efficiency. Quantitative proteomics identified novel PMP22 interacting proteins that may impact trafficking. Our results suggest that critical quality control decisions for unstable L16P PMP22 occur at earlier stages in the trafficking pathway than for the WT protein. Knock-out cell lines of likely PMP22 interactors led to the discovery that calnexin limits trafficking of stable PMP22 variants, UGGT1 promotes trafficking and RER1 limits trafficking of all PMP22 variants. This work establishes N-glycosylation as a key determinant of PMP22 retention in the ER, ultimately limiting forward surface-trafficking.
HostingRepository	PRIDE
AnnounceDate	2021-04-28
AnnouncementXML	Submission_2021-04-28_01:25:12.797.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Madison Wright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-13 11:09:35	ID requested
⏵ 1	2021-04-28 01:25:13	announced

Dataset with its publication pending

submitter keyword: protein quality control, Peripheral myelin protein 22, proteostasis, Charcot-Marie-Tooth disease, quantitative proteomics, protein folding

Charles R. Sanders
contact affiliation	Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, 37240, United States
contact email	chuck.sanders@vanderbilt.edu
lab head
Madison Wright
contact affiliation	Vanderbilt University Department of Chemistry
contact email	madison.t.wright@vanderbilt.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023091
     1. Label: PRIDE project
     2. Name: Glycosylation Limits Forward Trafficking of the Tetraspan Membrane Protein PMP22