RRC ID 55866
Author Chen SY, Ho CT, Liu WW, Lucanic M, Shih HM, Huang PH, Cheng HJ.
Title Regulation of axon repulsion by MAX-1 SUMOylation and AP-3.
Journal Proc Natl Acad Sci U S A
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 interactor 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.
Volume 115(35)
Pages E8236-E8245
Published 2018-8-28
DOI 10.1073/pnas.1804373115
PII 1804373115
PMID 30104385
PMC PMC6126772
MeSH Animals Axons / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Protein Transport / physiology Sumoylation / physiology* Transcription Factors / genetics Transcription Factors / metabolism*
IF 9.58
Times Cited 1
C.elegans tm2723