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      unc-33/CRMP and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting

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          The polarized distribution of neuronal proteins to axons and dendrites relies upon microtubule-binding proteins such as CRMP, directed motors such as kinesin UNC-104/Kif1A, and diffusion barriers such as ankyrin. The causative relationships between these molecules are unknown. We show here that Caenorhabditis elegans CRMP (UNC-33) acts early in neuronal development, together with ankyrin (UNC-44), to organize microtubule asymmetry and axon-dendrite sorting. In unc-33 and unc-44 mutants, axonal proteins are present in dendrites and vice versa, suggesting bidirectional failures of axon-dendrite identity. UNC-33 protein is localized to axons by unc-44, and enriched in a region that resembles the axon initial segment. unc-33 and unc-44 establish the asymmetric dynamics of axonal and dendritic microtubules; in their absence, microtubules are disorganized, the axonal kinesin UNC-104 invades dendrites, and inappropriate UNC-104 activity randomizes axonal protein sorting. We suggest that UNC-44 and UNC-33 direct polarized sorting through their global effects on neuronal microtubule organization.

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          Most cited references 40

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            Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map.

            Single nucleotide polymorphisms (SNPs) are valuable genetic markers of human disease. They also comprise the highest potential density marker set available for mapping experimentally derived mutations in model organisms such as Caenorhabditis elegans. To facilitate the positional cloning of mutations we have identified polymorphisms in CB4856, an isolate from a Hawaiian island that shows a uniformly high density of polymorphisms compared with the reference Bristol N2 strain. Based on 5.4 Mbp of aligned sequences, we predicted 6,222 polymorphisms. Furthermore, 3,457 of these markers modify restriction enzyme recognition sites ('snip-SNPs') and are therefore easily detected as RFLPs. Of these, 493 were experimentally confirmed by restriction digest to produce a snip-SNP map of the worm genome. A mapping strategy using snip-SNPs and bulked segregant analysis (BSA) is outlined. CB4856 is crossed into a mutant strain, and exclusion of CB4856 alleles of a subset of snip-SNPs in mutant progeny is assessed with BSA. The proximity of a linked marker to the mutation is estimated by the relative proportion of each form of the biallelic marker in populations of wildtype and mutant genomes. The usefulness of this approach is illustrated by the rapid mapping of the dyf-5 gene.
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              Neuronal polarity: from extracellular signals to intracellular mechanisms.

              After they are born and differentiate, neurons break their previous symmetry, dramatically change their shape, and establish two structurally and functionally distinct compartments - axons and dendrites - within one cell. How do neurons develop their morphologically and molecularly distinct compartments? Recent studies have implicated several signalling pathways evoked by extracellular signals as having essential roles in a number of aspects of neuronal polarization.

                Author and article information

                Nat Neurosci
                Nat. Neurosci.
                Nature neuroscience
                14 June 2014
                20 November 2011
                January 2012
                14 February 2015
                : 15
                : 1
                : 48-56
                [1 ] Laboratory of Neural Circuits and Behavior, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065
                [2 ] Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, California 94305, USA
                [3 ] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55406, USA
                [4 ] NCBS-TIFR, Bellary Road, Bangalore-560065, India
                Author notes
                [* ]Author for correspondence: cori@

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