Rodrigues, Elsa C.Grawenhoff, JuliaBaumann, SebastianLorenzon, NicolaMaurer, Sebastian2021-11-222021-11-222021Rodrigues EC, Grawenhoff J, Baumann SJ, Lorenzon N, Maurer SP. Mammalian neuronal mRNA transport complexes: the few knowns and the many unknowns. Front Integr Neurosci. 2021;15:692948. DOI: 10.3389/fnint.2021.6929481662-5145http://hdl.handle.net/10230/49028Hundreds of messenger RNAs (mRNAs) are transported into neurites to provide templates for the assembly of local protein networks. These networks enable a neuron to configure different cellular domains for specialized functions. According to current evidence, mRNAs are mostly transported in rather small packages of one to three copies, rarely containing different transcripts. This opens up fascinating logistic problems: how are hundreds of different mRNA cargoes sorted into distinct packages and how are they coupled to and released from motor proteins to produce the observed mRNA distributions? Are all mRNAs transported by the same transport machinery, or are there different adaptors or motors for different transcripts or classes of mRNAs? A variety of often indirect evidence exists for the involvement of proteins in mRNA localization, but relatively little is known about the essential activities required for the actual transport process. Here, we summarize the different types of available evidence for interactions that connect mammalian mRNAs to motor proteins to highlight at which point further research is needed to uncover critical missing links. We further argue that a combination of discovery approaches reporting direct interactions, in vitro reconstitution, and fast perturbations in cells is an ideal future strategy to unravel essential interactions and specific functions of proteins in mRNA transport processes.application/pdfeng© 2021 Rodrigues, Grawenhoff, Baumann, Lorenzon and Maurer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fnint.2021.692948RNA-binding proteinDyneinKinesinmRNA localizationmRNA traffickingNeuronsinfo:eu-repo/semantics/openAccess