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4 Publications

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    Eddy/Rivas Lab
    05/15/09 | Infernal 1.0: inference of RNA alignments.
    Nawrocki EP, Kolbe DL, Eddy SR
    Bioinformatics. 2009 May 15;25:1335-7. doi: 10.1093/bioinformatics/btp157

    SUMMARY: INFERNAL builds consensus RNA secondary structure profiles called covariance models (CMs), and uses them to search nucleic acid sequence databases for homologous RNAs, or to create new sequence- and structure-based multiple sequence alignments. AVAILABILITY: Source code, documentation and benchmark downloadable from http://infernal.janelia.org. INFERNAL is freely licensed under the GNU GPLv3 and should be portable to any POSIX-compliant operating system, including Linux and Mac OS/X.

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    Eddy/Rivas Lab
    05/15/09 | Local RNA structure alignment with incomplete sequence.
    Kolbe DL, Eddy SR
    Bioinformatics. 2009 May 15;25(10):1236-43. doi: 10.1093/bioinformatics/btp154

    Accuracy of automated structural RNA alignment is improved by using models that consider not only primary sequence but also secondary structure information. However, current RNA structural alignment approaches tend to perform poorly on incomplete sequence fragments, such as single reads from metagenomic environmental surveys, because nucleotides that are expected to be base paired are missing.

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    Svoboda Lab
    05/14/09 | Subcellular dynamics of type II PKA in neurons.
    Zhong H, Sia G, Sato TR, Gray NW, Mao T, Khuchua Z, Huganir RL, Svoboda K
    Neuron. 2009 May 14;62:363-74. doi: 10.1016/j.neuron.2009.03.013

    Protein kinase A (PKA) plays multiple roles in neurons. The localization and specificity of PKA are largely controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA in neurons and the roles of specific AKAPs are poorly understood. We imaged the distribution of type II PKA in hippocampal and cortical layer 2/3 pyramidal neurons in vitro and in vivo. PKA was concentrated in dendritic shafts compared to the soma, axons, and dendritic spines. This spatial distribution was imposed by the microtubule-binding protein MAP2, indicating that MAP2 is the dominant AKAP in neurons. Following cAMP elevation, catalytic subunits dissociated from the MAP2-tethered regulatory subunits and rapidly became enriched in nearby spines. The spatial gradient of type II PKA between dendritic shafts and spines was critical for the regulation of synaptic strength and long-term potentiation. Therefore, the localization and activity-dependent translocation of type II PKA are important determinants of PKA function.

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    Svoboda Lab
    05/01/09 | Myosin-dependent targeting of transmembrane proteins to neuronal dendrites.
    Lewis TL, Mao T, Svoboda K, Arnold DB
    Nature Neuroscience. 2009 May;12(5):568-76. doi: 10.1038/nn.2318

    The distinct electrical properties of axonal and dendritic membranes are largely a result of specific transport of vesicle-bound membrane proteins to each compartment. How this specificity arises is unclear because kinesin motors that transport vesicles cannot autonomously distinguish dendritically projecting microtubules from those projecting axonally. We hypothesized that interaction with a second motor might enable vesicles containing dendritic proteins to preferentially associate with dendritically projecting microtubules and avoid those that project to the axon. Here we show that in rat cortical neurons, localization of several distinct transmembrane proteins to dendrites is dependent on specific myosin motors and an intact actin network. Moreover, fusion with a myosin-binding domain from Melanophilin targeted Channelrhodopsin-2 specifically to the somatodendritic compartment of neurons in mice in vivo. Together, our results suggest that dendritic transmembrane proteins direct the vesicles in which they are transported to avoid the axonal compartment through interaction with myosin motors.

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