UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity.
| dc.contributor.author | Wang, Zheng | |
| dc.contributor.author | Linden, Lara M | |
| dc.contributor.author | Naegeli, Kaleb M | |
| dc.contributor.author | Ziel, Joshua W | |
| dc.contributor.author | Chi, Qiuyi | |
| dc.contributor.author | Hagedorn, Elliott J | |
| dc.contributor.author | Savage, Natasha S | |
| dc.contributor.author | Sherwood, David R | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2014-08-25T21:30:56Z | |
| dc.date.issued | 2014-09-01 | |
| dc.description.abstract | 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. | |
| dc.identifier | ||
| dc.identifier | jcb.201405026 | |
| dc.identifier.eissn | 1540-8140 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | The Rockefeller University Press | |
| dc.relation.ispartof | J Cell Biol | |
| dc.relation.isversionof | 10.1083/jcb.201405026 | |
| dc.subject | Actins | |
| dc.subject | Animals | |
| dc.subject | Caenorhabditis elegans | |
| dc.subject | Caenorhabditis elegans Proteins | |
| dc.subject | Cell Adhesion Molecules | |
| dc.subject | Cell Polarity | |
| dc.subject | Female | |
| dc.subject | Intracellular Signaling Peptides and Proteins | |
| dc.subject | Nerve Tissue Proteins | |
| dc.subject | Protein Multimerization | |
| dc.subject | Protein Stability | |
| dc.subject | Protein Transport | |
| dc.subject | Uterus | |
| dc.title | UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Sherwood, David R|0000-0002-4448-6917 | |
| pubs.author-url | ||
| pubs.begin-page | 619 | |
| pubs.end-page | 633 | |
| pubs.issue | 5 | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Biology | |
| pubs.organisational-group | Cell Biology | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Trinity College of Arts & Sciences | |
| pubs.publication-status | Published | |
| pubs.volume | 206 |
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