Genes required for cellular UNC-6/netrin localization in Caenorhabditis elegans.
UNC-6/Netrin is an evolutionarily conserved, secretory axon guidance molecule. In Caenorhabditis elegans, UNC-6 provides positional information to the axons of developing neurons, probably by establishing a concentration gradient from the ventral to the dorsal side of the animal. Although the proper localization of UNC-6 is important for accurate neuronal network formation, little is known about how its localization is regulated. Here, to examine the localization mechanism for UNC-6, we generated C. elegans expressing UNC-6 tagged with the fluorescent protein Venus and identified 13 genes, which are involved in the cellular localization of VenusUNC-6. For example, in unc-51, unc-14, and unc-104 mutants, the neurons showed an abnormal accumulation of VenusUNC-6 in the cell body and less than normal level of VenusUNC-6 in the axon. An aberrant accumulation of VenusUNC-6 in muscle cells was seen in unc-18 and unc-68 mutants. unc-51, unc-14, and unc-104 mutants also showed defects in the guidance of dorso-ventral axons, suggesting that the abnormal localization of UNC-6 disturbed the positional information it provides. We propose that these genes regulate the process of UNC-6 secretion: expression, maturation, sorting, transport, or exocytosis. Our findings provide novel insight into the localization mechanism of the axon guidance molecule UNC-6/Netrin.
Asakura
Taro
T
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Waga
Naoko
N
Ogura
Ken-Ichi
K
Goshima
Yoshio
Y
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002477:Cells / Q000378:metabolism; D005796:Genes; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism
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