Regulation of axon repulsion by MAX-1 SUMOylation and AP-3

Shih Yu Chen, Chun Ta Ho, Wei Wen Liu, Mark Lucanic, Hsiu Ming Shih, Pei Hsin Huang, Hwai-Jong Cheng

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5–mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5–mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3. Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3. Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive inter-actor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3–mediated trafficking and degradation of UNC-5 receptors during axon guidance.

Original languageEnglish (US)
Pages (from-to)E8236-E8245
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number35
DOIs
StatePublished - Aug 28 2018

Fingerprint

Sumoylation
Transcription Factor AP-1
Axons
Caenorhabditis elegans
Fluorescence Recovery After Photobleaching
Lysosomes
Proteolysis
Cues

Keywords

  • AP-3 complex
  • Axon guidance
  • C. elegans
  • MAX-1 SUMOylation
  • UNC-5 receptor

ASJC Scopus subject areas

  • General

Cite this

Chen, S. Y., Ho, C. T., Liu, W. W., Lucanic, M., Shih, H. M., Huang, P. H., & Cheng, H-J. (2018). Regulation of axon repulsion by MAX-1 SUMOylation and AP-3. Proceedings of the National Academy of Sciences of the United States of America, 115(35), E8236-E8245. https://doi.org/10.1073/pnas.1804373115

Regulation of axon repulsion by MAX-1 SUMOylation and AP-3. / Chen, Shih Yu; Ho, Chun Ta; Liu, Wei Wen; Lucanic, Mark; Shih, Hsiu Ming; Huang, Pei Hsin; Cheng, Hwai-Jong.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 35, 28.08.2018, p. E8236-E8245.

Research output: Contribution to journalArticle

Chen, SY, Ho, CT, Liu, WW, Lucanic, M, Shih, HM, Huang, PH & Cheng, H-J 2018, 'Regulation of axon repulsion by MAX-1 SUMOylation and AP-3', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 35, pp. E8236-E8245. https://doi.org/10.1073/pnas.1804373115
Chen, Shih Yu ; Ho, Chun Ta ; Liu, Wei Wen ; Lucanic, Mark ; Shih, Hsiu Ming ; Huang, Pei Hsin ; Cheng, Hwai-Jong. / Regulation of axon repulsion by MAX-1 SUMOylation and AP-3. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 35. pp. E8236-E8245.
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