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

Wang, Zheng, Linden, Lara M, Naegeli, Kaleb M, Ziel, Joshua W, Chi, Qiuyi, Hagedorn, Elliott J, Savage, Natasha S ORCID: 0000-0002-6831-6533 and Sherwood, David R
(2014) UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity. Journal of Cell Biology, 206 (5). pp. 619-633.

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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.

Item Type: Article
Additional Information: ## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords: Uterus, Animals, Caenorhabditis elegans, Actins, Intracellular Signaling Peptides and Proteins, Cell Adhesion Molecules, Caenorhabditis elegans Proteins, Nerve Tissue Proteins, Cell Polarity, Protein Transport, Female, Protein Multimerization, Protein Stability, Netrins
Depositing User: Symplectic Admin
Date Deposited: 07 Apr 2017 13:19
Last Modified: 19 Jan 2023 07:34
DOI: 10.1083/jcb.201405026
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3002233