Molecular motors: Directing traffic during RNA localization

Department of Molecular Biology, Cell Biology & Biochemistry, Brown University, Providence, RI, USA.
Critical Reviews in Biochemistry and Molecular Biology (Impact Factor: 7.71). 06/2011; 46(3):229-39. DOI: 10.3109/10409238.2011.572861
Source: PubMed


RNA localization, the enrichment of RNA in a specific subcellular region, is a mechanism for the establishment and maintenance of cellular polarity in a variety of systems. Ultimately, this results in a universal method for spatially restricting gene expression. Although the consequences of RNA localization are well-appreciated, many of the mechanisms that are responsible for carrying out polarized transport remain elusive. Several recent studies have illuminated the roles that molecular motor proteins play in the process of RNA localization. These studies have revealed complex mechanisms in which the coordinated action of one or more motor proteins can act at different points in the localization process to direct RNAs to their final destination. In this review, we discuss recent findings from several different systems in an effort to clarify pathways and mechanisms that control the directed movement of RNA.

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Available from: James Gagnon, Apr 09, 2014
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    • "The motor protein Kinesin-1 (hereafter Kinesin) is responsible for the transport of cargos in most cell types and plays a crucial role in germline and neuronal polarization. Mutations in the Drosophila melanogaster force-generating subunit of Kinesin, Kinesin heavy chain (KHC) result in defects in axonal transport (Hirokawa et al., 2010), localization of developmental determinants (Gagnon and Mowry, 2011) and movement of lipid droplets (Welte, 2009). A mouse model has also implicated Kinesin in axonal process growth (Karle et al., 2012). "
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    ABSTRACT: The major motor Kinesin-1 provides a key pathway for cell polarization through intracellular transport. Little is known about how Kinesin works in complex cellular surroundings. Several cargos associate with Kinesin via Kinesin light chain (KLC). However, KLC is not required for all Kinesin transport. A putative cargo-binding domain was identified in the C-terminal tail of fungal Kinesin heavy chain (KHC). The tail is conserved in animal KHCs and might therefore represent an alternative KLC-independent cargo-interacting region. By comprehensive functional analysis of the tail during Drosophila oogenesis we have gained an understanding of how KHC achieves specificity in its transport and how it is regulated. This is, to our knowledge, the first in vivo structural/functional analysis of the tail in animal Kinesins. We show that the tail is essential for all functions of KHC except Dynein transport, which is KLC dependent. These tail-dependent KHC activities can be functionally separated from one another by further characterizing domains within the tail. In particular, our data show the following. First, KHC is temporally regulated during oogenesis. Second, the IAK domain has an essential role distinct from its auto-inhibitory function. Third, lack of auto-inhibition in itself is not necessarily detrimental to KHC function. Finally, the ATP-independent microtubule-binding motif is required for cargo localization. These results stress that two unexpected highly conserved domains, namely the auto-inhibitory IAK and the auxiliary microtubule-binding motifs, are crucial for transport by Kinesin-1 and that, although not all cargos are conserved, their transport involves the most conserved domains of animal KHCs.
    Development 11/2013; 141(1). DOI:10.1242/dev.097592 · 6.46 Impact Factor
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    ABSTRACT: With the functional characterization of proteins advancing at fast pace, the notion that one protein performs different functions - often with no relation to each other - emerges as a novel principle of how cells work. Molecular motors are no exception to this new development. Here, we provide an account on recent findings revealing that microtubule motors are multifunctional proteins that regulate many cellular processes, in addition to their main function in transport. Some of these functions rely on their motor activity, but others are independent of it. Of the first category, we focus on the role of microtubule motors in organelle biogenesis, and in the remodeling of the cytoskeleton, especially through the regulation of microtubule dynamics. Of the second category, we discuss the function of microtubule motors as static anchors of the cargo at the destination, and their participation in regulating signaling cascades by modulating interactions between signaling proteins, including transcription factors. We also review atypical forms of transport, such as the cytoplasmic streaming in the oocyte, and the movement of cargo by microtubule fluctuations. Our goal is to provide an overview of these unexpected functions of microtubule motors, and to incite future research in this expanding field.
    Archives of Biochemistry and Biophysics 01/2012; 520(1):17-29. DOI:10.1016/ · 3.02 Impact Factor
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    ABSTRACT: Microtubule-dependent trafficking is essential in moving mRNAs over long distances. This transport mechanism regulates important cellular events such as determining polarity and local protein secretion. Key examples are developmental and neuronal processes studied in Drosophila melanogaster, Xenopus laevis as well as in mammalian cells. A simple eukaryotic system to uncover basic mechanisms was missing. Fungal models are generally well suited for this purpose, since transgenic strains can be generated easily by homologous recombination allowing in vivo studies at native expression levels. Substantial advances in understanding Ustilago maydis showed that this fungus fulfils important criteria to serve as model for microtubule-dependent mRNA trafficking. Here, we summarize progress focusing on target mRNAs, RNA localization elements, RNA-binding proteins, mRNPs, molecular motors and microtubule organization. This serves as the basis to discuss the novel mechanism of mRNP hitchhiking on endosomes as well as an unexpected link to unconventional secretion with its implications for applied sciences.
    RNA biology 03/2012; 9(3):261-8. DOI:10.4161/rna.19432 · 4.97 Impact Factor
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