PXD037387

PXD037387 is an original dataset announced via ProteomeXchange.

Title	The protein complex of kinesin motor KIF1C and its hereditary spastic paraplegia associated mutant G102A
Description	Regulated local translation, RNA transport and protein localization are critical for spatio-temporal gene expression in neurons. The localization of mRNA and subsequent local protein synthesis contribute to neuronal functions like synaptogenesis, synapse pruning, axon guidance, axonal regeneration and synaptic plasticity. Thus, mutations in motor proteins and subsequent cargo transport failure lead to motoneuron diseases. The kinesin family member 1 C has been shown to play a role in different cargo transport alongside the microtubule network, but the pathomechanisms behind KIF1C deficiency mediated motoneuron diseases has not been deciphered yet. Additionally, the exon junction complex has been suggested as a molecular link between splicing and cytoplasmic mRNA localization and local translation. Here we identified KIF1C as a EJC transporter in neuronal cells. We investigated the KIF1C proteome in differentiated SH-SY5Y cells and found an interaction of KIF1C with EJC components and other RNA-binding proteins in KIF1C overexpressing SH-SY5Y cells. The interaction could be validated via immunoprecipitation and an endogenous eIF4A3 co-immunoprecipitation. The co-localization of eIF4A3 and RBM8A with wildtpye KIF1C at protrusions of SH-SY5Ys further confirms the interaction. The mislocalization of eIF4A3 and RMB8A due to KIF1C mutation suggests a transport of the EJC by KIF1C. Furthermore, the interaction of KIF1C with PABPC1 and EJC components is RNA mediated. We additionally demonstrate via complex capture with KIF1C overexpressing HEK293 cells that KIF1C interacts with RNA itself. We therefore suggest the interaction of KIF1C not only with the EJC, but with a complex containing RNA and the EJC. Hence KIF1C is a transporter of mRNA and the EJC.
HostingRepository	PRIDE
AnnounceDate	2023-12-28
AnnouncementXML	Submission_2023-12-28_11:15:06.533.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karsten Boldt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-13 14:56:07	ID requested
⏵ 1	2023-12-28 11:15:07	announced

Nagel M, Noss M, Xu J, Horn N, Ueffing M, Boldt K, Schuele R, The kinesin motor KIF1C is a putative transporter of the exon junction complex in neuronal cells. RNA, 29(1):55-68(2022) [pubmed]

10.1261/rna.079426.122;

submitter keyword: hereditary spastic paraplegia, KIF1C, neuronal cells

Dr. Karsten Boldt
contact affiliation	Institute for ophthalmic research University of Tuebingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Karsten Boldt
contact affiliation	Medical Bioanalytics
contact email	karsten.boldt@uni-tuebingen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037387
     1. Label: PRIDE project
     2. Name: The protein complex of kinesin motor KIF1C and its hereditary spastic paraplegia associated mutant G102A