title: TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance.
abstract: TRIpartite Motif (TRIM) family proteins are ring finger domain-containing, multi-domain proteins implicated in many biological processes. Members of the TRIM-9/C-I subfamily of TRIM proteins, including TRIM-9, MID1 and MID2, have neuronal functions and are associated with neurological diseases. To explore whether the functions of C-I TRIM proteins are conserved in invertebrates, we analyzed Caenorhabditis elegans and Drosophila trim-9 mutants. C. elegans trim-9 mutants exhibit defects in the ventral guidance of hermaphrodite specific neuron (HSN) and the touch neuron AVM. Further genetic analyses indicate that TRIM-9 participates in the UNC-6-UNC-40 attraction pathway. Asymmetric distribution of UNC-40 during HSN development is normal in trim-9 mutants. However, the asymmetric localization of MIG-10, a downstream effector of UNC-40, is abolished in trim-9 mutants. These results suggest that TRIM-9 functions upstream of MIG-10 in the UNC-40 pathway. Moreover, we showed that TRIM-9 exhibits E3 ubiquitin ligase activity in vitro and this activity is important for TRIM-9 function in vivo. Additionally, we found that Drosophila trim-9 is required for the midline attraction of a group of sensory neuron axons. Over-expression of the Netrin/UNC-6 receptor Frazzled suppresses the guidance defects in trim-9 mutants. Our study reveals an evolutionarily conserved function of TRIM-9 in the UNC-40/Frazzled-mediated UNC-6/Netrin attraction pathway.
authors.affiliation: Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Song
authors.initials: S
authors.lastname: Song
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Ge
authors.forename: Jinbo
authors.initials: J
authors.lastname: Wang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.forename: Sanyuan
authors.initials: S
authors.lastname: Tang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Bi
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Xie
authors.forename: Xun
authors.initials: X
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism; D019143:Evolution, Molecular; D057850:Hermaphroditic Organisms / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075386:Netrin Receptors; D000075385:Netrins; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D021381:Protein Transport; D054829:RING Finger Domains; D011956:Receptors, Cell Surface / Q000378:metabolism; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C105812:Mig-10 protein, C elegans; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075385:Netrins; D011956:Receptors, Cell Surface; C551653:TRIM-9 protein, C elegans; C102174:UNC-40 protein, C elegans; C078146:UNC-6 protein, C elegans; C000617310:fra protein, Drosophila; D044767:Ubiquitin-Protein Ligases