Role of Unc51.1 and its binding partners in CNS axon outgrowth. Genes Dev

Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10021-6399, USA.
Genes & Development (Impact Factor: 12.64). 04/2004; 18(5):541-58. DOI: 10.1101/gad.1151204
Source: PubMed

ABSTRACT Previous studies showed that the serine/threonine kinase Unc51.1 is one of the earliest genes in neuronal differentiation and is required for granule cell axon formation. To examine the mechanism of Unc51.1 regulation of axon extension, we have identified two direct binding partners. The first, SynGAP, a negative regulator of Ras, is expressed within axons and growth cones of developing granule cells. Overexpression of SynGAP blocks neurite outgrowth by a mechanism that involves Ras-like GTPase cascade. The second binding partner is a PDZ domain-containing scaffolding protein, Syntenin, that binds Rab5 GTPase, the activity of which is attenuated by SynGAP. Thus, our results demonstrate that the Unc51.1-containing protein complex governs axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.

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    • "induced cohesiveness of epidermal stem cells through direct interaction of Delta1 with MDA-9/syntenin that maintains Delta1 on the cell surface (Estrach et al. 2007). Moreover, MDA-9/syntenin is involved in synaptic transmission via interaction with glutamate receptors, and axonal outgrowth by interacting with Unc51.1 and Rab5 (Hirbec et al. 2002; Enz and Croci 2003; Tomoda et al. 2004). "
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    Journal of molecular histology 11/2012; 44(2). DOI:10.1007/s10735-012-9468-1 · 1.98 Impact Factor
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    • "Ulk2 is thought to promote process extension through stimulation of early endosome trafficking at growing neurite tips. Ulk2 has been shown to increase early endosome formation by activation of the small GTPase Rab5 (Tomoda et al., 2004). In axons, early endosomes that contain activated growth factor receptors (e.g. "
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    ABSTRACT: Studies of the zebrafish epithalamus have provided recent insights into the development of left-right brain asymmetry, which is crucial to normal human brain function. The habenular nuclei of zebrafish are robustly asymmetric, with dense elaboration of neuropil only in the left lateral subnucleus. Because this feature is tightly correlated with asymmetric expression of K(+) channel tetramerization domain-containing proteins 12.1 and 12.2 (Kctd12.1/12.2), we screened for Kctd12.1-interacting proteins to identify molecular mechanisms leading to neuropil asymmetry, and uncovered a novel interaction between Kctd12.1 and Unc-51-like kinase 2 (Ulk2). We show here that knockdown of Ulk2 or overexpression of Kctd12 proteins reduces asymmetric neuropil elaboration. Conversely, overexpression of Ulk2 or mutation of kctd12 genes causes excess neuropil elaboration. We conclude that Ulk2 activity promotes neuropil elaboration while Kctd12 proteins limit Ulk2 activity asymmetrically. This work describes a regulatory mechanism for neuronal process extension that may be conserved in other developmental contexts in addition to the epithalamus.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 07/2011; 31(27):9869-78. DOI:10.1523/JNEUROSCI.0435-11.2011 · 6.75 Impact Factor
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    • "ULK1 has a kinase activity and phosphorylates mATG13 and FIP200 (Ganley et al., 2009; Jung et al., 2009). In C. elegans, Unc51 has been shown to be involved in axonal elongation (Tomoda et al., 2004). "
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    Experimental and Molecular Medicine 04/2011; 43(5):231-74. DOI:10.3858/emm.2011.43.5.032 · 2.46 Impact Factor
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