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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, Z; Linden, LM; Naegeli, KM; Ziel, JW; Chi, Q; Hagedorn, EJ; Savage, NS; Sherwood, DR

Published Date

  • September 2014

Published In

Volume / Issue

  • 206 / 5

Start / End Page

  • 619 - 633

PubMed ID

  • 25154398

Pubmed Central ID

  • 25154398

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

International Standard Serial Number (ISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.201405026

Language

  • eng