TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance

Song Song; Qinglan Ge; Jinbo Wang; Haiyang Chen; Sanyuan Tang; Junfeng Bi; Xia Li; Qi Xie; Xun Huang

doi:10.1016/j.jcg.2010.12.004

Volume 38 Issue 1

Jan. 2011

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TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance

doi: 10.1016/j.jcg.2010.12.004

Song Song^{a, c, #},
Qinglan Ge^{a, c, #},
Jinbo Wang^{a, c, #},
Haiyang Chen^{a, c},
Sanyuan Tang^b,
Junfeng Bi^{a, c},
Xia Li^a,
Qi Xie^b,
Xun Huang^a

a
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
b
State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
c
Graduate School of Chinese Academy of Sciences, Beijing 100049, China

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Corresponding author: E-mail address: xhuang@genetics.ac.cn (Xun Huang)
Received Date: 2010-11-26
Accepted Date: 2010-12-07
Rev Recd Date: 2010-12-06

Available Online: 2011-02-19

Publish Date: 2011-01-20

Abstract

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.
- TRIM-9,
- Axon guidance,
- UNC-6/Netrin,
- UNC-40/Frazzled

These authors contributed equally to this work.

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References(43)

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