A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs.
Sebastian BaumannArtem KomissarovMaria GiliVerena RuprechtStefan WieserSebastian P MaurerPublished in: Science advances (2020)
Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such 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. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a 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 3'UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.
Keyphrases
- gene expression
- spinal cord
- spinal cord injury
- escherichia coli
- genome wide analysis
- binding protein
- single cell
- dna methylation
- induced apoptosis
- palliative care
- stem cells
- mesenchymal stem cells
- cell proliferation
- oxidative stress
- genome wide
- bone marrow
- signaling pathway
- cell death
- endoplasmic reticulum stress
- optic nerve
- genetic diversity
- solid state