hiw

Summary

Gene Symbol: hiw
Description: highwire
Alias: CG32592, CG9041, CG9049, Dmel\CG32592, Hiw, highwire, CG32592-PA, CG32592-PB, hiw-PA, hiw-PB
Species: fruit fly
Products:     hiw

Top Publications

  1. DiAntonio A, Haghighi A, Portman S, Lee J, Amaranto A, Goodman C. Ubiquitination-dependent mechanisms regulate synaptic growth and function. Nature. 2001;412:449-52 pubmed
    ..5) also produces synaptic overgrowth and dysfunction. Genetic interactions between fat facets and highwire, a negative regulator of synaptic growth that has structural homology to a family of ubiquitin ligases, suggest ..
  2. Keshishian H. Is synaptic homeostasis just wishful thinking?. Neuron. 2002;33:491-2 pubmed
    ..2002) and Marqués et al. present evidence that BMP receptors may also influence the development of synapses. The results suggest a novel mechanism for regulating neuronal growth and synaptic homeostasis during development. ..
  3. Wu C, Daniels R, DiAntonio A. DFsn collaborates with Highwire to down-regulate the Wallenda/DLK kinase and restrain synaptic terminal growth. Neural Dev. 2007;2:16 pubmed
    ..Genetic studies have demonstrated that the ubiquitin ligase Highwire restrains synaptic terminal growth by down-regulating the MAP kinase kinase kinase Wallenda/dual leucine zipper ..
  4. Murthy V, Han S, Beauchamp R, Smith N, Haddad L, Ito N, et al. Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex. J Biol Chem. 2004;279:1351-8 pubmed
    ..Although Pam function(s) are yet to be defined, the highly conserved Pam homologs, HIW (Drosophila) and RPM-1 (Caenorhabditis elegans), are neuron-specific proteins that regulate synaptic growth...
  5. Wu C, Wairkar Y, Collins C, DiAntonio A. Highwire function at the Drosophila neuromuscular junction: spatial, structural, and temporal requirements. J Neurosci. 2005;25:9557-66 pubmed
    b>Highwire is a huge, evolutionarily conserved protein that is required to restrain synaptic growth and promote synaptic transmission at the Drosophila neuromuscular junction...
  6. Shin J, DiAntonio A. Highwire regulates guidance of sister axons in the Drosophila mushroom body. J Neurosci. 2011;31:17689-700 pubmed publisher
    Axons often form synaptic contacts with multiple targets by extending branches along different paths. PHR (Pam/Highwire/RPM-1) family ubiquitin ligases are important regulators of axon development, with roles in axon outgrowth, target ..
  7. Massaro C, Pielage J, Davis G. Molecular mechanisms that enhance synapse stability despite persistent disruption of the spectrin/ankyrin/microtubule cytoskeleton. J Cell Biol. 2009;187:101-17 pubmed publisher
  8. Shen W, Ganetzky B. Autophagy promotes synapse development in Drosophila. J Cell Biol. 2009;187:71-9 pubmed publisher
    ..Autophagy induces an NMJ overgrowth phenotype closely resembling that of highwire (hiw), an E3 ubiquitin ligase mutant...
  9. Collins C, Wairkar Y, Johnson S, DiAntonio A. Highwire restrains synaptic growth by attenuating a MAP kinase signal. Neuron. 2006;51:57-69 pubmed
    b>Highwire is an extremely large, evolutionarily conserved E3 ubiquitin ligase that negatively regulates synaptic growth at the Drosophila NMJ. Highwire has been proposed to restrain synaptic growth by downregulating a synaptogenic signal...

More Information

Publications58

  1. McCabe B, Hom S, Aberle H, Fetter R, Marques G, Haerry T, et al. Highwire regulates presynaptic BMP signaling essential for synaptic growth. Neuron. 2004;41:891-905 pubmed
    b>Highwire (Hiw), a putative RING finger E3 ubiquitin ligase, negatively regulates synaptic growth at the neuromuscular junction (NMJ) in Drosophila...
  2. Wan H, DiAntonio A, Fetter R, Bergstrom K, Strauss R, Goodman C. Highwire regulates synaptic growth in Drosophila. Neuron. 2000;26:313-29 pubmed
    ..A primary walking behavior screen followed by a secondary anatomical screen led to the identification of the highwire (hiw) gene. In hiw mutants, the specificity of motor axon pathfinding and synapse formation appears normal...
  3. Xiong X, Hao Y, Sun K, Li J, Li X, Mishra B, et al. The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein. PLoS Biol. 2012;10:e1001440 pubmed publisher
    ..Here, using a Drosophila injury model, we have identified a highly conserved E3 ubiquitin ligase, Highwire (Hiw), as an important regulator of axonal and synaptic degeneration...
  4. Xiong X, Wang X, Ewanek R, Bhat P, DiAntonio A, Collins C. Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury. J Cell Biol. 2010;191:211-23 pubmed publisher
    ..Wnd is regulated by a conserved E3 ubiquitin ligase, named Highwire (Hiw) in Drosophila. Injury induces a rapid increase in Wnd protein concomitantly with a decrease in Hiw protein...
  5. Keshishian H, Kim Y. Orchestrating development and function: retrograde BMP signaling in the Drosophila nervous system. Trends Neurosci. 2004;27:143-7 pubmed
    ..Together, the results suggest that retrograde growth factor signaling by BMPs integrates neuromuscular development and function at both local and global levels in the animal. ..
  6. Kuo C, Zhu S, Younger S, Jan L, Jan Y. Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Neuron. 2006;51:283-90 pubmed
    ..Thus, in addition to uncovering E2/E3 ubiquitinating enzymes for dendrite pruning, this study provides a mechanistic link between UPS and the apoptotic machinery in regulating neuronal process remodeling. ..
  7. West R, Lu Y, Marie B, Gao F, Sweeney S. Rab8, POSH, and TAK1 regulate synaptic growth in a Drosophila model of frontotemporal dementia. J Cell Biol. 2015;208:931-47 pubmed publisher
    ..Our data uncover Rab8, POSH, and TAK1 as regulators of synaptic growth responses and point to recycling endosome as a key compartment for synaptic growth regulation during neurodegenerative processes. ..
  8. Wong C, Palmieri M, Li J, Akhmedov D, Chao Y, Broadhead G, et al. Diminished MTORC1-Dependent JNK Activation Underlies the Neurodevelopmental Defects Associated with Lysosomal Dysfunction. Cell Rep. 2015;12:2009-20 pubmed publisher
    ..Our findings provide an explanation for the neurodevelopmental deficits in LSDs and suggest an actionable target for treatment. ..
  9. Dobson A, Chaston J, Newell P, Donahue L, Hermann S, Sannino D, et al. Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster. Nat Commun. 2015;6:6312 pubmed publisher
    ..These interactions with the microbiota are probably conserved across animals, including humans. ..
  10. Chang Q, Balice Gordon R. Highwire, rpm-1, and futsch: balancing synaptic growth and stability. Neuron. 2000;26:287-90 pubmed
  11. Haag Liautard C, Dorris M, Maside X, Macaskill S, Halligan D, Houle D, et al. Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature. 2007;445:82-5 pubmed
    ..2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction. ..
  12. Miller D, Ballard S, Ganetzky B. Analysis of synaptic growth and function in Drosophila with an extended larval stage. J Neurosci. 2012;32:13776-86 pubmed publisher
    ..growth (adding >50 boutons/NMJ), and this growth remains under the control of the canonical regulators Highwire and the TGF?/BMP pathway...
  13. Brink D, GILBERT M, Xie X, Petley Ragan L, Auld V. Glial processes at the Drosophila larval neuromuscular junction match synaptic growth. PLoS ONE. 2012;7:e37876 pubmed publisher
    ..Increasing synaptic size through elevated temperature or the highwire mutation increased the extent of glial processes at the NMJ and conversely blocking synaptic activity and size ..
  14. Hong X, Doddapaneni H, Comeron J, Rodesch M, Halvensleben H, Nien C, et al. Microarray-based capture of novel expressed cell type-specific transfrags (CoNECT) to annotate tissue-specific transcription in Drosophila melanogaster. G3 (Bethesda). 2012;2:873-82 pubmed publisher
    ..Ovary and testis isotigs over 200 bp have been deposited with the GenBank Transcriptome Shotgun Assembly Sequence Database as bioproject no.PRJNA89451 (accession nos. JV208106–JV230865). ..
  15. Huang C, Zheng X, Zhao H, Li M, Wang P, Xie Z, et al. A permissive role of mushroom body ?/? core neurons in long-term memory consolidation in Drosophila. Curr Biol. 2012;22:1981-9 pubmed publisher
    ..Although, with the ease of genetic manipulation, many genes and brain structures have been related to LTM formation, it is still an important task to identify new components and reveal the mechanisms underlying LTM regulation...
  16. Jin Y. Synaptogenesis: insights from worm and fly. Curr Opin Neurobiol. 2002;12:71-9 pubmed
  17. Bao H, Berlanga M, Xue M, Hapip S, Daniels R, Mendenhall J, et al. The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila. Mol Cell Neurosci. 2007;34:662-78 pubmed
    ..These findings shed new light on a possible role for Flamingo in progressive neurodegenerative diseases. ..
  18. Doumanis J, Wada K, Kino Y, Moore A, Nukina N. RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation. PLoS ONE. 2009;4:e7275 pubmed publisher
    ..Newly identified modifiers including genes related to nuclear transport, nucleotide processes, and signaling, may be involved in polyglutamine aggregate formation and Huntington disease cascades. ..
  19. Zhao H, Zheng X, Yuan X, Wang L, Wang X, Zhong Y, et al. ben Functions with scamp during synaptic transmission and long-term memory formation in Drosophila. J Neurosci. 2009;29:414-24 pubmed publisher
    ..We also provide evidence that BEN interacts genetically in both synaptic transmission and LTM formation with SCAMP, a synaptic protein known to be involved in vesicle recycling. ..
  20. Neukomm L, Burdett T, Gonzalez M, Zuchner S, Freeman M. Rapid in vivo forward genetic approach for identifying axon death genes in Drosophila. Proc Natl Acad Sci U S A. 2014;111:9965-70 pubmed publisher
    ..of principle we screened the X chromosome and identified a collection eight recessive and two dominant alleles of highwire, a ubiquitin E3 ligase required for axon degeneration...
  21. Fischer J, Overstreet E. Fat facets does a Highwire act at the synapse. Bioessays. 2002;24:13-6 pubmed
    ..A recent report by DiAntonio et al. shows that two ubiquitin pathway proteins, Highwire and Fat facets, may be mutually antagonistic regulators of presynaptic growth at the Drosophila neuromuscular ..
  22. McDermott S, Yang L, Halstead J, Hamilton R, Meignin C, Davis I. Drosophila Syncrip modulates the expression of mRNAs encoding key synaptic proteins required for morphology at the neuromuscular junction. RNA. 2014;20:1593-606 pubmed publisher
    ..a number of mRNAs encoding proteins with key synaptic functions, including msp-300, syd-1, neurexin-1, futsch, highwire, discs large, and α-spectrin...
  23. Brace E, Wu C, Valakh V, DiAntonio A. SkpA restrains synaptic terminal growth during development and promotes axonal degeneration following injury. J Neurosci. 2014;34:8398-410 pubmed publisher
    ..Regulation of this pathway is in part through the E3 ubiquitin ligase Highwire (Hiw), which targets Wnd/DLK for degradation to limit MAPK signaling...
  24. Zhan L, Xie Q, Tibbetts R. Opposing roles of p38 and JNK in a Drosophila model of TDP-43 proteinopathy reveal oxidative stress and innate immunity as pathogenic components of neurodegeneration. Hum Mol Genet. 2015;24:757-72 pubmed publisher
    ..Reducing Wnd gene dosage or overexpressing its antagonist highwire partially rescued TDP-43-associated premature lethality...
  25. Godena V, Romano G, Romano M, Appocher C, Klima R, Buratti E, et al. TDP-43 regulates Drosophila neuromuscular junctions growth by modulating Futsch/MAP1B levels and synaptic microtubules organization. PLoS ONE. 2011;6:e17808 pubmed publisher
    ..Moreover, we observed that TDP-43 physically interacts with futsch mRNA and that its RNA binding capacity is required to prevent futsch down regulation and synaptic defects. ..
  26. Soustelle L, Giangrande A. Novel gcm-dependent lineages in the postembryonic nervous system of Drosophila melanogaster. Dev Dyn. 2007;236:2101-8 pubmed
    ..It is also expressed in a thoracic glial lineage and in neurons of the ventral nerve cord (VNC). Finally, while gcm is required for gliogenesis in medulla and VNC, it does not seem to be required for the generation of VNC neurons. ..
  27. Tian X, Li J, Valakh V, DiAntonio A, Wu C. Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in post-mitotic neurons. Nat Neurosci. 2011;14:1267-75 pubmed publisher
    The evolutionarily conserved Highwire (Hiw)/Drosophila Fsn E3 ubiquitin ligase complex is required for normal synaptic morphology during development and axonal regeneration after injury...
  28. van Roessel P, Elliott D, Robinson I, Prokop A, Brand A. Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell. 2004;119:707-18 pubmed
    ..In neurons, the APC/C controls synaptic size via a downstream effector Liprin-alpha; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor. ..
  29. Mozer B, Sandstrom D. Drosophila neuroligin 1 regulates synaptic growth and function in response to activity and phosphoinositide-3-kinase. Mol Cell Neurosci. 2012;51:89-100 pubmed publisher
    ..Synaptic overgrowth, triggered by neuronal hyperactivity, absence of the E3 ubiquitin ligase highwire, and increased phosphoinositide-3-kinase (PI3K) signaling in motor neurons reduced synaptic DNlg1 levels...
  30. Uthaman S, Godenschwege T, Murphey R. A mechanism distinct from highwire for the Drosophila ubiquitin conjugase bendless in synaptic growth and maturation. J Neurosci. 2008;28:8615-23 pubmed publisher
    ..that Ben is not a part of the signal transduction pathway involving the well characterized ubiquitin ligase highwire. We conclude that Bendless functions as a novel developmental switch that permits the transition from axonal ..
  31. Wang X, Sterne G, Ye B. Regulatory mechanisms underlying the differential growth of dendrites and axons. Neurosci Bull. 2014;30:557-68 pubmed publisher
    ..The knowledge of these underlying molecular mechanisms not only expands our understanding about how neural circuits are wired, but also provides insights that will aid in the rational design of therapies for neurological diseases. ..
  32. Strauss R. The central complex and the genetic dissection of locomotor behaviour. Curr Opin Neurobiol. 2002;12:633-8 pubmed
  33. Sulkowski M, Han T, Ott C, Wang Q, Verheyen E, Lippincott Schwartz J, et al. A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction. PLoS Genet. 2016;12:e1005810 pubmed publisher
    ..Thus, BMP pathway may monitor synapse activity then function to adjust synapse growth and maturation during development. ..
  34. Crona F, Holmqvist P, Tang M, Singla B, Vakifahmetoglu Norberg H, Fantur K, et al. The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos. Dev Biol. 2015;407:173-81 pubmed publisher
    ..We conclude that the transcriptional co-regulator Brakeless can either activate or repress transcription depending on context. ..
  35. Wisotzkey R, Quijano J, Stinchfield M, Newfeld S. New gene evolution in the bonus-TIF1-?/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network. Mol Biol Evol. 2014;31:2309-21 pubmed publisher
    ..Overall our data reveal that the architecture of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the vertebrate lineage, after separation from flies, via the incorporation of new genes. ..
  36. Valakh V, Walker L, Skeath J, DiAntonio A. Loss of the spectraplakin short stop activates the DLK injury response pathway in Drosophila. J Neurosci. 2013;33:17863-73 pubmed publisher
    ..We further show that, unlike mutations in the PHR ligase Highwire, loss of function of shot activates DLK without a concomitant increase in the levels of DLK...
  37. Harvey J, Brunger H, Middleton C, Hill J, Sevdali M, Sweeney S, et al. Neuromuscular control of a single twitch muscle in wild type and mutant Drosophila, measured with an ergometer. Invert Neurosci. 2008;8:63-70 pubmed publisher
    ..The initial responses of synaptic growth mutants (highwire and spinster) do not differ from wild type, as expected on the homeostatic hypothesis...
  38. Merino C, Penney J, González M, Tsurudome K, Moujahidine M, O Connor M, et al. Nemo kinase interacts with Mad to coordinate synaptic growth at the Drosophila neuromuscular junction. J Cell Biol. 2009;185:713-25 pubmed publisher
    ..Based on our findings, we propose a model in which phosphorylation of Mad by Nmo ensures normal accumulation and distribution of Mad and thereby fine tunes BMP signaling in motor neurons. ..
  39. Sanyal S, Ramaswami M. Spinsters, synaptic defects, and amaurotic idiocy. Neuron. 2002;36:335-8 pubmed
    ..This study provides important new information at an intersection of several disciplines, including membrane traffic, lipid organization, synaptic signaling, and neurodegenerative lysosomal storage disease...
  40. Klinedinst S, Wang X, Xiong X, Haenfler J, Collins C. Independent pathways downstream of the Wnd/DLK MAPKKK regulate synaptic structure, axonal transport, and injury signaling. J Neurosci. 2013;33:12764-78 pubmed publisher
  41. Watts R, Hoopfer E, Luo L. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron. 2003;38:871-85 pubmed
    ..Our findings suggest that some forms of axon pruning during development may share similarities with degeneration of axons in response to injury. ..
  42. Broadie K, Richmond J. Establishing and sculpting the synapse in Drosophila and C. elegans. Curr Opin Neurobiol. 2002;12:491-8 pubmed
    ..Glutamate acts as a negative regulator of its cognate postsynaptic receptor to sculpt receptor field size. Finally, protein translation and degradation regulation emerge as possible key regulators of synaptic efficacy. ..
  43. Sreedharan J, Neukomm L, Brown R, Freeman M. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Curr Biol. 2015;25:2130-6 pubmed publisher
    ..In addition to delineating genetic factors that modify TDP-43 toxicity, these results establish the Drosophila adult leg as a valuable new tool for the in vivo study of adult MN phenotypes. ..
  44. Nijhof B, Castells Nobau A, Wolf L, Scheffer de Gooyert J, Monedero I, Torroja L, et al. A New Fiji-Based Algorithm That Systematically Quantifies Nine Synaptic Parameters Provides Insights into Drosophila NMJ Morphometry. PLoS Comput Biol. 2016;12:e1004823 pubmed publisher
    ..Our study sets the stage for systems morphometry approaches at the well-studied Drosophila NMJ. ..
  45. Borgen M, Rowland K, Boerner J, Lloyd B, Khan A, MURPHEY R. Axon Termination, Pruning, and Synaptogenesis in the Giant Fiber System of Drosophila melanogaster Is Promoted by Highwire. Genetics. 2017;205:1229-1245 pubmed publisher
    The ubiquitin ligase Highwire has a conserved role in synapse formation...
  46. Kim J, Wang X, Coolon R, Ye B. Dscam expression levels determine presynaptic arbor sizes in Drosophila sensory neurons. Neuron. 2013;78:827-38 pubmed publisher
    ..Our findings uncover a function of Dscam in presynaptic size control and provide insights into how dysregulated Dscam may contribute to the pathogenesis of neurological disorders. ..
  47. Wang X, Kim J, Bazzi M, Robinson S, Collins C, Ye B. Bimodal control of dendritic and axonal growth by the dual leucine zipper kinase pathway. PLoS Biol. 2013;11:e1001572 pubmed publisher
    ..We find that the dual leucine zipper kinase (DLK) signaling pathway in Drosophila, which consists of Highwire and Wallenda and controls axonal growth, regeneration, and degeneration, is also involved in dendritic growth in ..
  48. Bao H, Reist N, Zhang B. The Drosophila epsin 1 is required for ubiquitin-dependent synaptic growth and function but not for synaptic vesicle recycling. Traffic. 2008;9:2190-205 pubmed publisher
    ..However, Lqf is not a substrate of the Highwire (Hiw) E3 ubiquitin ligase; neither is it required for synapse overgrowth in hiw mutants...
  49. Milton V, Jarrett H, Gowers K, Chalak S, Briggs L, Robinson I, et al. Oxidative stress induces overgrowth of the Drosophila neuromuscular junction. Proc Natl Acad Sci U S A. 2011;108:17521-6 pubmed publisher
    ..Our data describe a previously unexplored link between oxidative stress and synapse overgrowth via the JNK signaling pathway. ..