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bioRxiv · 10.1101/701250

A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

Baumann, S.·Komissarov, A.·Gili, M. L.·Ruprecht, V.·Wieser, S.·Maurer, S. P.
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Abstract

Through the asymmetric distribution of mRNAs cells spatially regulate gene expression to create cyto-plasmic domains with specialized functions. In mammalian neurons, mRNA localization is required for essential processes as cell polarization, migration and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. Here, we report the first reconstitution of a mammalian mRNA transport system revealing that the tumour suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localised {beta}-actin and {beta}2B-tubulin mRNAs which are linked to a heterotrimeric kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2 and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal for the first time a minimal set of proteins capable of driving kinesin-based, mammalian mRNA transport.

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Baumann, S., Komissarov, A., Gili, M. L., Ruprecht, V., Wieser, S., Maurer, S. P.. 2019-07-26. A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs. https://doi.org/10.1101/701250

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