Regulatory machinery of UNC-33 Ce-CRMP localization in neurites during neuronal development in Caenorhabditis elegans.
In Caenorhabditis elegans, unc-33 encodes an orthologue of the vertebrate collapsin response mediator protein (CRMP) family. We previously reported that CRMP-2 accumulated in the distal part of the growing axon of vertebrate neurons and played critical roles in axon elongation. unc-33 mutants show axonal outgrowth defects in several neurons. It has been reported that UNC-33 accumulates in neurites, whereas a missense mutation causes the mislocalization of UNC-33 from neurites to cell body, which suggests that the localization of UNC-33 in neurites is important for axonal outgrowth. However, it is unclear how UNC-33 accumulates in neurites and regulates neuronal development. In this study, to understand the regulatory mechanisms of localization of UNC-33 in neurites, we screened for the mutants that were involved in the localization of UNC-33, and identified three mutants: unc-14 (RUN domain protein), unc-51 (ULK kinase) and unc-116 (kinesin heavy chain). UNC-14 is known to associate with UNC-51. UNC-116 forms a complex with KLC-2 as Kinesin-1, a microtubule-dependent motor complex. We found that UNC-33 interacted with UNC-14 and KLC-2 in vivo. These results suggest that the UNC-14/UNC-51 complex and Kinesin-1 are involved in the localization of UNC-33 in neurites.
Tsuboi
Daisuke
D
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Aichi, Japan.
Hikita
Takao
T
Qadota
Hiroshi
H
Amano
Mutsuki
M
Kaibuchi
Kozo
K
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D016547:Kinesins / Q000378:metabolism; D008845:Microinjections; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; C107406:UNC-14 protein, C elegans; C502665:klc-1 protein, C elegans; C078652:unc-33 protein, C elegans; D016547:Kinesins