mRNA Transport in Dendrites: RNA Granules, Motors, and Tracks

Hirokawa, Nobutaka

doi:10.1523/jneurosci.1821-06.2006

Cited by 159 publications

(123 citation statements)

References 31 publications

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“…Given that it is now well established that protein synthesis does occur in axons and synaptic terminals (Hirokawa, 2006;Martin and Zukin, 2006;Schuman et al, 2006;Wells, 2006), it is conceivable that MBNL1 may participate in the transport of mRNAs for some photoreceptor synaptic proteins toward their terminals, much as MBNL2 does in the case of the transport of integrin-␣3 mRNA toward the areas of focal adhesion complexes (Adereth et al, 2005). We are currently investigating this possibility.…”

Section: C) E-jmentioning

confidence: 99%

Developmental regulation of muscleblind‐like (MBNL) gene expression in the chicken embryo retina

Hu¹,

Wahlin²,

McNally³

et al. 2007

Developmental Dynamics

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Muscleblind-like (MBNL) is a CCCH zinc finger-containing RNA-binding protein required for the development of both muscle and photoreceptors in Drosophila; it is conserved evolutionarily, and it is associated in humans with the muscular disease myotonic dystrophy. Its role in the development of vertebrate retinal cells, however, remains unknown. As an initial approach to its investigation, we have cloned three chick muscleblind genes, characterized their isoforms, and examined their expression patterns in the chick embryo retina. The relative levels of expression of the MBNL genes increased during embryonic development. In situ hybridization (ISH) showed that the three MBNL mRNAs had widespread patterns of expression at all the developmental stages examined. Of interest, the temporal and spatial patterns of protein expression, detected by immunocytochemistry with antibodies against MBNL1 and MBNL2, were much more restricted than those seen by ISH. At early stages (ED5-7), for example, MBNL1 and MBNL2 mRNAs were present throughout the retina, but immunoreactivity for the corresponding proteins was largely restricted to the periphery of the optic cup (presumptive iris/ciliary epithelium/ciliary margin zone). MBNL1 and MBNL2 immunoreactivity became detectable at the fundus at later stages, but was limited to a very small subset of the cells that had ISH signals for the cognate mRNAs (particularly ganglion cells and photoreceptors). Within photoreceptors, MBNL1 and MBNL2 immunoreactivity first appeared in their inner segments; MBNL2 remained there, but MBNL1 became subsequently localized to their synaptic terminals. These expression patterns are consistent with the possibility that MBNLs may regulate photoreceptor development in the chick retina, much as MBL does in Drosophila, and suggest that the expression of MBNL1 and MBNL2 may be regulated posttranscriptionally. Developmental Dynamics 237: 286 -296, 2008.

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Section: C) E-jmentioning

confidence: 99%

Developmental regulation of muscleblind‐like (MBNL) gene expression in the chicken embryo retina

Hu¹,

Wahlin²,

McNally³

et al. 2007

Developmental Dynamics

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“…Many membranous organelles and protein complexes are normally transported anterograde within neuronal axons to the presynaptic terminal, and details of the motors, adaptors and cargoes have received significant attention (Hirokawa and Takemura, 2005;Goldstein and Yang, 2000) In contrast, much less is known about the regulation of transport of non-membrane bound particles in neurons (Brown, 2003). For example, mRNAs and proteins associated with the mRNA and cytoskeletal polymers require transport motors (presumably kinesin-related) and associated proteins for their delivery to dendrites and axons (Bassell et al, 1998;Hirokawa, 2006;Yan and Brown, 2005;Wang and Brown, 2002;Galbraith and Gallant, 2000). Identification of the specific motors and associated motor proteins that participate with Us9 in viral capsid and DNA anterograde transport is extremely important but likely to be a challenging task (Baas and Qiang, 2005).…”

Section: How Viral Dna Is Axonally Transportedmentioning

confidence: 99%

Viral regulation of the long distance axonal transport of herpes simplex virus nucleocapsid

et al. 2007

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Abstract-Many membranous organelles and protein complexes are normally transported anterograde within axons to the presynaptic terminal, and details of the motors, adaptors and cargoes have received significant attention. Much less is known about the transport in neurons of non-membrane bound particles, such as mRNAs and their associated proteins. We propose that herpes simplex virus type 1 (HSV) can be used to study the detailed mechanisms regulating long distance transport of particles in axons. A critical step in the transmission of HSV from one infected neuron to the next is the polarized anterograde axonal transport of viral DNA from the host infected nerve cell body to the axon terminal. Using the in vivo mouse retinal ganglion cell model infected with wild type virus or a mutant strain that lacks the protein Us9, we found that Us9 protein was necessary for long distance anterograde axonal transport of viral nucleocapsid (DNA surrounded by capsid proteins), but unnecessary for transport of virus envelope. Thus, we conclude that nucleocapsid can be transported independently down axons via a Us9-dependent mechanism.

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“…Where studied, the localization of mRNAs to axons or dendrites has been shown to depend on cisacting localization elements (LEs) usually found in the 3′ UTR, although occasionally present in the coding sequence or 5′ UTR (1,2,9). These cis-acting mRNA LEs recruit specific transacting RNA binding proteins, and the resulting messenger ribonucleoproteins are packaged into RNA transport granules that interact with molecular motors to be delivered to their final subcellular destination (10)(11)(12).…”

mentioning

confidence: 99%

Identification of a cis-acting element that localizes mRNA to synapses

Meer

Wang²,

Sangmok³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Messenger RNA (mRNA) localization and regulated translation can spatially restrict gene expression to each of the thousands of synaptic compartments formed by a single neuron. Although cisacting RNA elements have been shown to direct localization of mRNAs from the soma into neuronal processes, less is known about signals that target transcripts specifically to synapses. In Aplysia sensory-motor neuronal cultures, synapse formation rapidly redistributes the mRNA encoding the peptide neurotransmitter sensorin from neuritic shafts into synapses. We find that the export of sensorin mRNA from soma to neurite and the localization to synapse are controlled by distinct signals. The 3′ UTR is sufficient for export into distal neurites, whereas the 5′ UTR is required for concentration of reporter mRNA at synapses. We have identified a 66-nt element in the 5′ UTR of sensorin that is necessary and sufficient for synaptic mRNA localization. Mutational and chemical probing analyses are consistent with a role for secondary structure in this process.M essenger RNA (mRNA) localization and regulated translation provide a means of spatially restricting gene expression within distinct subcellular compartments. In the brain, local protein synthesis is critical to the development and experience-driven refinement of neural circuits, playing roles in axon guidance, synaptogenesis, and synaptic plasticity (1, 2). A large but select population of transcripts localizes to axons and dendrites (3-8), indicating that local translation subserves diverse cell biological functions. Where studied, the localization of mRNAs to axons or dendrites has been shown to depend on cisacting localization elements (LEs) usually found in the 3′ UTR, although occasionally present in the coding sequence or 5′ UTR (1, 2, 9). These cis-acting mRNA LEs recruit specific transacting RNA binding proteins, and the resulting messenger ribonucleoproteins are packaged into RNA transport granules that interact with molecular motors to be delivered to their final subcellular destination (10-12).In situ hybridization studies in neurons indicate that localized mRNAs in neurons are targeted to distinct subcellular compartments and domains within neuronal processes. For example, MAP2 mRNA concentrates within proximal dendrites, whereas calcium-calmodulin dependent protein kinase IIα (CaMKIIα) mRNA extends to distal dendrites (13). mRNA localization also seems to be dynamically regulated during development and with activity. In mature neurons, β-actin mRNA localizes to dendrites, and its concentration to distal dendrites is stimulated by depolarization (14). Stimuli that activate NMDA or neurotrophic receptor tyrosine kinase 2 (TrkB) receptors drive specific BDNF mRNA isoforms into distal dendrites of hippocampal neurons (15). High-frequency stimulation of perforant path projections to the dentate gyrus has been shown to direct localization of the mRNA encoding the immediate-early gene Arc selectively and specifically to activated dendritic lamina (16) and to drive localizati...

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mRNA Transport in Dendrites: RNA Granules, Motors, and Tracks

Cited by 159 publications

References 31 publications

Developmental regulation of muscleblind‐like (MBNL) gene expression in the chicken embryo retina

Developmental regulation of muscleblind‐like (MBNL) gene expression in the chicken embryo retina

Viral regulation of the long distance axonal transport of herpes simplex virus nucleocapsid

Identification of a cis-acting element that localizes mRNA to synapses

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