UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity.
Repository Usage Stats
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.
Caenorhabditis elegans Proteins
Cell Adhesion Molecules
Intracellular Signaling Peptides and Proteins
Nerve Tissue Proteins
Published Version (Please cite this version)10.1083/jcb.201405026
Publication InfoChi, Q; Hagedorn, EJ; Linden, Lara M; Naegeli, KM; Savage, NS; Sherwood, David R; ... Ziel, JW (2014). UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity. J Cell Biol, 206(5). pp. 619-633. 10.1083/jcb.201405026. Retrieved from https://hdl.handle.net/10161/9026.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
More InfoShow full item record
Showing items related by title, author, creator, and subject.
LKB1 Loss induces characteristic patterns of gene expression in human tumors associated with NRF2 activation and attenuation of PI3K-AKT. Kaufman, Jacob; Amann, Joseph M; Park, Kyungho; Arasada, Rajeswara Rao; Li, Haotian; Shyr, Yu; Carbone, David P (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014-06)Inactivation of serine/threonine kinase 11 (STK11 or LKB1) is common in lung cancer, and understanding the pathways and phenotypes altered as a consequence will aid the development of targeted therapeutic strategies. Gene ...
Amino acid permeases require COPII components and the ER resident membrane protein Shr3p for packaging into transport vesicles in vitro. Kuehn, Margarethe Joanna; Ljungdahl, PO; Schekman, R (J Cell Biol, 1996-11)In S. cerevisiae lacking SHR3, amino acid permeases specifically accumulate in membranes of the endoplasmic reticulum (ER) and fail to be transported to the plasma membrane. We examined the requirements of transport of the ...
Hawes, BE; Lefkowitz, Robert J; Touhara, K; van Biesen, T (Proc Natl Acad Sci U S A, 1995-09-26)The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, ...