UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity.
Data(s) |
01/09/2014
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Formato |
619 - 633 |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/25154398 jcb.201405026 J Cell Biol, 2014, 206 (5), pp. 619 - 633 http://hdl.handle.net/10161/9026 1540-8140 |
Relação |
J Cell Biol 10.1083/jcb.201405026 |
Tipo |
Journal Article |
Cobertura |
United States |
Resumo |
The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin). Time-lapse analyses revealed that UNC-40 clusters assemble, disassemble, and reform at periodic intervals in different regions of the cell membrane. This oscillatory behavior indicates that UNC-40 clusters through a mechanism involving interlinked positive (formation) and negative (disassembly) feedback. We show that endogenous UNC-6 and ectopically provided UNC-6 orient and stabilize UNC-40 clustering. Furthermore, the UNC-40-binding protein MADD-2 (a TRIM family protein) promotes ligand-independent clustering and robust UNC-40 polarization toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin. |
Idioma(s) |
ENG |
Palavras-Chave | #Actins #Animals #Caenorhabditis elegans #Caenorhabditis elegans Proteins #Cell Adhesion Molecules #Cell Polarity #Female #Intracellular Signaling Peptides and Proteins #Nerve Tissue Proteins #Protein Multimerization #Protein Stability #Protein Transport #Uterus |