A Ligand-Gated Association between Cytoplasmic Domains of UNC5 and DCC Family Receptors Converts Netrin-Induced Growth Cone Attraction to Repulsion

@article{Hong1999ALA,
  title={A Ligand-Gated Association between Cytoplasmic Domains of UNC5 and DCC Family Receptors Converts Netrin-Induced Growth Cone Attraction to Repulsion},
  author={Kyonsoo Hong and Lindsay Hinck and Makoto Nishiyama and Mu-Ming Poo and Marc Tessier‐Lavigne and Elke Stein},
  journal={Cell},
  year={1999},
  volume={97},
  pages={927-941}
}
Netrins are bifunctional: they attract some axons and repel others. Netrin receptors of the Deleted in Colorectal Cancer (DCC) family are implicated in attraction and those of the UNC5 family in repulsion, but genetic evidence also suggests involvement of the DCC protein UNC-40 in some cases of repulsion. To test whether these proteins form a receptor complex for repulsion, we studied the attractive responses of Xenopus spinal axons to netrin-1, which are mediated by DCC. We show that… 
Netrin Binds Discrete Subdomains of DCC and UNC5 and Mediates Interactions between DCC and Heparin*
TLDR
The results suggest that interactions between DCC and heparin are probably mediated by netrin, and it is demonstrated that a loop on the fifth fibronectin type III repeat of DCC previously implicated in mediating interactions withHeparin is important for sNetrin binding.
Surface Expression of the Netrin Receptor UNC5H1 Is Regulated through a Protein Kinase C-Interacting Protein/Protein Kinase-Dependent Mechanism
TLDR
It is demonstrated that surface expression of UNC5H1 is regulated in neurons by protein interacting with C kinase-1 (PICK1) and protein kinase C (PKC), and shown that one mechanism by which cells control their response to netrin-1 is by changing the surface availability of receptors.
Protein Interacting with C-Kinase 1/Protein Kinase Cα-Mediated Endocytosis Converts Netrin-1-Mediated Repulsion to Attraction
TLDR
It is shown that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis, and PKCα-stimulated internalization of UNC5A alters the functional response of developing hippocampal axons to netrin-1.
The Adaptor Protein Nck-1 Couples the Netrin-1 Receptor DCC (Deleted in Colorectal Cancer) to the Activation of the Small GTPase Rac1 through an Atypical Mechanism*
TLDR
Evidence is provided for an important role of mammalian Nck-1 in a novel signaling pathway from an extracellular guidance cue to changes in the actin-based cytoskeleton responsible for axonal guidance.
Binding of DCC by Netrin-1 to Mediate Axon Guidance Independent of Adenosine A2B Receptor Activation
TLDR
DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation and the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cy toplasmsic domain multimerization.
Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor
TLDR
The results indicate that the growth-promoting function of netrin-1 may require a receptor complex containing DCC and A2b, a G-protein-coupled receptor that induces cAMP accumulation on binding adenosine.
The dependence receptors DCC and UNC5H as a link between neuronal guidance and survival
TLDR
The possible roles of DCC and UNC5H pro‐apoptotic activities in both nervous system development and tumorigenesis are concluded.
Mapping Netrin Receptor Binding Reveals Domains of Unc5 Regulating Its Tyrosine Phosphorylation
Netrin and its receptors Unc5 and deleted in colorectal carcinoma (DCC) regulate axon guidance and cell migration. We defined domains involved in the interactions between netrin-1, DCC, and Unc5c. We
The Netrin family of guidance factors: emphasis on Netrin-1 signalling
TLDR
Several signal transduction pathways and effector molecules have been implicated in the response to Netrin-1: small Rho-GTPases, MAP-Kinases, second messengers and the Microtubule Associated Protein 1B (MAP1B).
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