PXD028074-1

PXD028074 is an original dataset announced via ProteomeXchange.

Title	Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage
Description	Nuclear pore complexes (NPCs) discriminate non-specific macromolecules from importin and exportin receptors, collectively termed karyopherins (Kaps), that mediate nucleocytoplasmic transport. This selective barrier function is attributed to the behavior of intrinsically disordered phenylalanine-glycine nucleoporins (FG Nups) that guard the NPC channel. However, NPCs in vivo are typically enriched with different Kaps, and how they impact on the NPC barrier remains unknown. Here, we show that two major Kaps, importinβ1/karyopherinβ1 (Kapβ1) and exportin 1/chromosomal maintenance 1 (CRM1) are required to fortify NPC barrier function in vivo. Their enrichment at the NPC is sustained by promiscuous binding interactions with the FG Nups resulting in a compensatory mechanism that is constrained by their respective cellular abundances and different binding kinetics as evidenced for another Kap, Importin-5. Hence, Kapβ1 and CRM1 engage in a balancing act to reinforce NPC barrier function. Consequently, NPC malfunction and nucleocytoplasmic leakage result from poor Kap enrichment.
HostingRepository	PRIDE
AnnounceDate	2022-01-26
AnnouncementXML	Submission_2022-01-26_02:15:58.370.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028074
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alexander Schmidt
SpeciesList	scientific name: Canis lupus familiaris; NCBI TaxID: 9615;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-23 07:49:38	ID requested
⏵ 1	2022-01-26 02:15:58	announced

Dataset with its publication pending

submitter keyword: PRM, iBAQ, Karyopherin, LC-MS, NPC, MDCK

Alexander Schmidt
contact affiliation	Proteomics Core Facility, Biozentrum, University of Basel, Switzerland
contact email	alex.schmidt@unibas.ch
lab head
Alexander Schmidt
contact affiliation	Proteomics Core Facility
contact email	alex.schmidt@unibas.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028074
     1. Label: PRIDE project
     2. Name: Karyopherin enrichment and compensation fortifies the nuclear pore complex against nucleocytoplasmic leakage