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UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity.

dc.contributor.author Chi, Q
dc.contributor.author Hagedorn, EJ
dc.contributor.author Linden, Lara M
dc.contributor.author Naegeli, KM
dc.contributor.author Savage, NS
dc.contributor.author Sherwood, David R
dc.contributor.author Wang, Z
dc.contributor.author Ziel, JW
dc.coverage.spatial United States
dc.date.accessioned 2014-08-25T21:30:56Z
dc.date.issued 2014-09-01
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/25154398
dc.identifier jcb.201405026
dc.identifier.uri https://hdl.handle.net/10161/9026
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.language eng
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
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/25154398
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
dc.identifier.eissn 1540-8140


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