PXD031012

PXD031012 is an original dataset announced via ProteomeXchange.

Title	ALS-Associated KIF5A Mutations Abolish Autoinhibition Resulting in a Toxic Gain of Function
Description	Understanding the pathogenic mechanisms of disease mutations is critical to advancing treatments. ALS-associated mutations in the gene encoding the microtubule motor KIF5A result in skipping of exon 27 (KIF5AΔExon27) and the encoding of a protein with a novel 39-amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C-terminus of mutant KIF5A results in a constitutively active state. Further, mutant KIF5A possesses novel protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative ALS mutations result in a toxic gain of function in the intracellular motor KIF5A that disrupts intracellular trafficking and neuronal homeostasis.
HostingRepository	PRIDE
AnnounceDate	2022-06-09
AnnouncementXML	Submission_2022-06-09_03:09:06.911.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031012
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Desiree Baron
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X; nanoACQUITY UPLC

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-16 23:07:35	ID requested
⏵ 1	2022-06-09 03:09:07	announced

Baron DM, Fenton AR, Saez-Atienzar S, Giampetruzzi A, Sreeram A, Shankaracharya, Keagle PJ, Doocy VR, Smith NJ, Danielson EW, Andresano M, McCormack MC, Garcia J, Bercier V, Van Den Bosch L, Brent JR, Fallini C, Traynor BJ, Holzbaur ELF, Landers JE, ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function. Cell Rep, 39(1):110598(2022) [pubmed]

submitter keyword: Human, ALS, KIF5A, interactors

John Edward Landers
contact affiliation	Department of Neurology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
contact email	John.Landers@umassmed.edu
lab head
Desiree Baron
contact affiliation	UMASS Medical School
contact email	Desiree.Baron@umassmed.edu
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/2022/06/PXD031012

PRIDE project URI

• PRIDE
  1. PXD031012
     1. Label: PRIDE project
     2. Name: ALS-Associated KIF5A Mutations Abolish Autoinhibition Resulting in a Toxic Gain of Function