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

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)

These authors contributed equally to this work.

摘要

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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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