Drosophila IKK-related kinase Ik2 and Katanin p60-like 1 regulate dendrite pruning of sensory neuron during metamorphosis

Pruning is a widely observed mechanism for developing nervous systems to refine their circuitry. During metamorphosis, certain Drosophila sensory neurons undergo large-scale dendrite pruning to remove their larval branches before regeneration of their adult dendrites. Dendrite pruning involves dendrite severing, followed with debris removal. Little is known about the molecular mechanisms underlying dendrite severing. Here, we show that both the Ik2 kinase and Katanin p60-like 1 (Kat-60L1) of the Katanin family of microtubule severing proteins are required for dendrite severing. Mutant neurons with disrupted Ik2 function have diminished ability in severing their larval dendrites in pupae. Conversely, premature activation of Ik2 triggers precocious dendrite severing in larvae, revealing a critical role of Ik2 in initiating dendrite severing. We found a role for Kat-60L1 in facilitating dendrite severing by breaking microtubule in proximal dendrites, where the dendrites subsequently separate from the soma. Our study thus implicates Ik2 and Kat-60L1 in dendrite severing that involves local microtubule disassembly.

[1]  J. Gaertig,et al.  Katanin regulates dynamics of microtubules and biogenesis of motile cilia , 2007, The Journal of cell biology.

[2]  Darren W. Williams,et al.  Local caspase activity directs engulfment of dendrites during pruning , 2006, Nature Neuroscience.

[3]  Masatomo Kobayashi,et al.  Drosophila IKK-Related Kinase Regulates Nonapoptotic Function of Caspases via Degradation of IAPs , 2006, Cell.

[4]  R. Ueda,et al.  IKKɛ Regulates F Actin Assembly and Interacts with Drosophila IAP1 in Cellular Morphogenesis , 2006, Current Biology.

[5]  Y. Jan,et al.  Identification of E2/E3 Ubiquitinating Enzymes and Caspase Activity Regulating Drosophila Sensory Neuron Dendrite Pruning , 2006, Neuron.

[6]  Eric D. Hoopfer,et al.  Wlds Protection Distinguishes Axon Degeneration following Injury from Naturally Occurring Developmental Pruning , 2006, Neuron.

[7]  Sen-Lin Lai,et al.  Genetic mosaic with dual binary transcriptional systems in Drosophila , 2006, Nature Neuroscience.

[8]  K. Anderson,et al.  Drosophila Ik2, a member of the IκB kinase family, is required for mRNA localization during oogenesis , 2006, Development.

[9]  L. Qiang,et al.  Tau Protects Microtubules in the Axon from Severing by Katanin , 2006, The Journal of Neuroscience.

[10]  Y. Jan,et al.  Dendrite-specific remodeling of Drosophila sensory neurons requires matrix metalloproteases, ubiquitin-proteasome, and ecdysone signaling. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Takaaki Hirotsu,et al.  MBR-1, a Novel Helix-Turn-Helix Transcription Factor, Is Required for Pruning Excessive Neurites in Caenorhabditis elegans , 2005, Current Biology.

[12]  Darren W. Williams,et al.  Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons , 2005, Development.

[13]  L. Luo,et al.  Axon retraction and degeneration in development and disease. , 2005, Annual review of neuroscience.

[14]  L. Qiang,et al.  Regulation of Microtubule Severing by Katanin Subunits during Neuronal Development , 2005, The Journal of Neuroscience.

[15]  L. Luo,et al.  Developmentally programmed remodeling of the Drosophila olfactory circuit , 2005, Development.

[16]  K. Zinn,et al.  Drosophila Spastin Regulates Synaptic Microtubule Networks and Is Required for Normal Motor Function , 2004, PLoS biology.

[17]  G. Johnson,et al.  Tau phosphorylation in neuronal cell function and dysfunction , 2004, Journal of Cell Science.

[18]  Jaime Grutzendler,et al.  Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches , 2004, Nature Neuroscience.

[19]  Andrei N Lupas,et al.  Phylogenetic analysis of AAA proteins. , 2004, Journal of structural biology.

[20]  Feng Chen,et al.  A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac , 2004, Nature Genetics.

[21]  James R. Knight,et al.  A Protein Interaction Map of Drosophila melanogaster , 2003, Science.

[22]  Chenggang Lu,et al.  The Caenorhabditis elegans microtubule-severing complex MEI-1/MEI-2 katanin interacts differently with two superficially redundant beta-tubulin isotypes. , 2003, Molecular biology of the cell.

[23]  Aaron Ciechanover,et al.  The Ubiquitin Proteasome System in Neurodegenerative Diseases Sometimes the Chicken, Sometimes the Egg , 2003, Neuron.

[24]  Zhigang He,et al.  Involvement of the Ubiquitin-Proteasome System in the Early Stages of Wallerian Degeneration , 2003, Neuron.

[25]  Liqun Luo,et al.  Axon Pruning during Drosophila Metamorphosis Evidence for Local Degeneration and Requirement of the Ubiquitin-Proteasome System , 2003, Neuron.

[26]  Y. Jan,et al.  Dendrites of Distinct Classes of Drosophila Sensory Neurons Show Different Capacities for Homotypic Repulsion , 2003, Current Biology.

[27]  F. McNally,et al.  Katanin-mediated microtubule severing can be regulated by multiple mechanisms. , 2002, Cell motility and the cytoskeleton.

[28]  Yuh Nung Jan,et al.  Tiling of the Drosophila epidermis by multidendritic sensory neurons. , 2002, Development.

[29]  H Li,et al.  Huntingtin Aggregate-Associated Axonal Degeneration is an Early Pathological Event in Huntington's Disease Mice , 2001, The Journal of Neuroscience.

[30]  L. Luo,et al.  Cell-Autonomous Requirement of the USP/EcR-B Ecdysone Receptor for Mushroom Body Neuronal Remodeling in Drosophila , 2000, Neuron.

[31]  R. Carthew,et al.  Heritable gene silencing in Drosophila using double-stranded RNA , 2000, Nature Biotechnology.

[32]  F. McNally,et al.  Two domains of p80 katanin regulate microtubule severing and spindle pole targeting by p60 katanin. , 2000, Journal of cell science.

[33]  L. Luo,et al.  Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast. , 1999, Development.

[34]  Liqun Luo,et al.  Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis , 1999, Neuron.

[35]  R. Vale,et al.  Katanin, a Microtubule-Severing Protein, Is a Novel AAA ATPase that Targets to the Centrosome Using a WD40-Containing Subunit , 1998, Cell.

[36]  G. Drewes,et al.  Phosphorylation of Microtubule-associated Proteins MAP2 and MAP4 by the Protein Kinase p110 , 1996, The Journal of Biological Chemistry.

[37]  J. Truman,et al.  Metamorphosis of the central nervous system of Drosophila. , 1990, Journal of neurobiology.

[38]  R. Ueda,et al.  IKK epsilon regulates F actin assembly and interacts with Drosophila IAP1 in cellular morphogenesis. , 2006, Current biology : CB.

[39]  K. Fröhlich.  An AAA family tree. , 2001, Journal of cell science.