PXD013939

PXD013939 is an original dataset announced via ProteomeXchange.

Title	PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport
Description	The kinesin-3 KIF1C is a fast organelle transporter implicated in the transport of dense core vesicles in neurons and the delivery of integrins to cell adhesions. Here we report the mechanisms of autoinhibition and release that control the activity of KIF1C. We show that the microtubule binding surface of KIF1C motor domain interacts with its stalk and that these autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21. The FERM domain of PTPN21 stimulates dense core vesicle transport in primary hippocampal neurons and rescues integrin trafficking in KIF1C-depleted cells. In vitro, human full-length KIF1C is a processive, plus-end directed motor. Its landing rate onto microtubules increases in the presence of either PTPN21 FERM domain or the cargo adapter Hook3 that binds the same region of KIF1C tail. This autoinhibition release mechanism allows cargo-activated transport and might enable motors to participate in bidirectional cargo transport without undertaking a tug-of-war.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:56:50.834.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hamdi Hussain
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-20 07:45:48	ID requested
1	2019-06-24 07:38:48	announced
2	2019-06-27 02:01:23	announced	Updated publication reference for PubMed record(s): 31217419.
⏵ 3	2024-10-22 04:56:52	announced	2024-10-22: Updated project metadata.

Siddiqui N, Zwetsloot AJ, Bachmann A, Roth D, Hussain H, Brandt J, Kaverina I, Straube A, PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport. Nat Commun, 10(1):2693(2019) [pubmed]

10.1038/s41467-019-10644-9;

submitter keyword: Autoinhibition, PTPN21, HOOK3,KIF1C

Anne Straube
contact affiliation	Centre for Mechanochemical Cell Biology, University of Warwick, Coventry, CV4 7AL, UK
contact email	anne@mechanochemistry.org
lab head
Hamdi Hussain
contact affiliation	University of Warwick
contact email	hamdi.hussain@warwick.ac.uk
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/2019/06/PXD013939

PRIDE project URI

• PRIDE
  1. PXD013939
     1. Label: PRIDE project
     2. Name: PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport