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APC couples neuronal mRNAs to multiple kinesins, EB1 and shrinking microtubule ends for bidirectional mRNA motility
- Publication Year :
- 2022
- Publisher :
- Cold Spring Harbor Laboratory, 2022.
-
Abstract
- Understanding where in the cytoplasm mRNAs are translated is increasingly recognized as being as important as knowing the timing and level of protein expression. mRNAs are localized via active motor-driven transport along microtubules (MTs) but the underlying essential factors and dynamic interactions are largely unknown. Using biochemical in vitro reconstitutions with purified mammalian proteins, multicolor TIRF-microscopy, and interaction kinetics measurements, we show that adenomatous polyposis coli (APC) enables kinesin-1- and kinesin-2-based mRNA transport, and that APC is an ideal adaptor for long-range mRNA transport as it forms highly stable complexes with 3'UTR fragments of several neuronal mRNAs (APC-RNPs). The kinesin-1 KIF5A binds and transports several neuronal mRNP components such as FMRP, PURα and mRNA fragments weakly, whereas the transport frequency of the mRNA fragments is significantly increased by APC. APC-RNP-motor complexes can assemble on MTs, generating highly processive mRNA transport events. We further find that end-binding protein 1 (EB1) recruits APC-RNPs to dynamically growing MT ends and APC-RNPs track shrinking MTs, producing MT minus-end-directed RNA motility due to the high dwell times of APC on MTs. Our findings establish APC as a versatile mRNA-kinesin adaptor and a key factor for the assembly and bidirectional movement of neuronal transport mRNPs. This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2017-85361-P], [PID2020-114870GB-I00], [BFU2015-62550-ERC], the Ministerio de Ciencia, Innovación y Universidades and Fondo Social Europeo (FSE) [PRE2018-084501], Juan de la Cierva-Incorporación Program [IJCI-2015-25994], the Human Frontiers in Science Program (HFSP) [RGY0083/2016], and the European Research Council (ERC) [H2020-MSCA-IF-2014-659271.]. We further acknowledge the support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa’ [SEV-2012-0208].
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....34ff25c43e9558895b93a3547e9ded1d
- Full Text :
- https://doi.org/10.1101/2022.07.01.498380