PXD042325

PXD042325 is an original dataset announced via ProteomeXchange.

Title	N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and the nuclear envelope
Description	Fibroblast growth factor receptor 1 (FGFR1) is a heavily N-glycosylated cell surface receptor tyrosine kinase, which in conjunction with fibroblast growth factors (FGFs) transmits signals through the plasma membrane. The balanced FGF/FGFR1 signaling is crucial for the development and homeostasis of human body and aberrant FGFR1 is often observed in various cancers. Besides predominant localization to the plasma membrane, FGFR1 was also detected inside cells, mainly in the nuclear lumen, where it modulates gene expression. However, the exact mechanism of FGFR1 nuclear transport is still unknown. In this study, we generated a glycosylation-free mutant of FGFR1, FGFR1.GF, and demonstrate that it is primarily localized to the nuclear envelope. We show that reintroduction of N-glycans in the D3 domain cannot redirect FGFR1 to the plasma membrane nor exclude the receptor from the nuclear envelope. Reestablishment of N-glycans of the D2 domain largely inhibits FGFR1 accumulation in the nuclear envelope, but receptor still accumulates inside the cell, mainly in the ER. Only the simultaneous presence of N-glycans of the D2 and D3 domains of FGFR1 supports the efficient transport of FGFR1 to the plasma membrane. Intracellular FGFR1.GF displays high level of autoactivation, suggesting the presence of nuclear FGFR1 signaling that is FGF independent. Using mass spectrometry and proximity ligation assay we identified novel binding partners of the nuclear envelope-localized FGFR1, providing insights into its cellular functions. Taken together, our data define N-glycosylation of FGFR1 as a significant regulator of FGFR1 kinase activity, and most importantly a switchable signal for FGFR1 trafficking between the nuclear envelope and the plasma membrane, which, due to the spatial restrictions, shapes the FGFR1 interactome and cellular function.
HostingRepository	PRIDE
AnnounceDate	2023-10-24
AnnouncementXML	Submission_2023-10-24_12:53:56.101.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD042325
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	AgataMalinowska
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-18 07:07:05	ID requested
⏵ 1	2023-10-24 12:53:56	announced

10.6019/PXD042325;

Gregorczyk P, Por, ę, bska N, Ż, ukowska D, Chor, ą, ż, ewska A, G, ę, daj A, Malinowska A, Otlewski J, Zakrzewska M, Opali, ń, ski Ł, N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and nuclear envelope. Cell Commun Signal, 21(1):177(2023) [pubmed]

submitter keyword: FGFR1, trafficking,Glycosylation, label-free, nucleus, signaling

ŁukaszOpaliński
contact affiliation	Faculty of Biotechnology, Department of Protein Engineering, University of Wroclaw, Wroclaw, Poland
contact email	lukasz.opalinski@uwr.edu.pl
lab head
AgataMalinowska
contact affiliation	IBB PAS
contact email	esme@ibb.waw.pl
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD042325

PRIDE project URI

• PRIDE
  1. PXD042325
     1. Label: PRIDE project
     2. Name: N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and the nuclear envelope