Publication Date:
2001-03-10
Description:
Netrins stimulate and orient axon growth through a mechanism requiring receptors of the DCC family. It has been unclear, however, whether DCC proteins are involved directly in signaling or are mere accessory proteins in a receptor complex. Further, although netrins bind cells expressing DCC, direct binding to DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stein, E -- Zou, Y -- Poo , M -- Tessier-Lavigne, M -- New York, N.Y. -- Science. 2001 Mar 9;291(5510):1976-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0452, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11239160" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Axons/*physiology
;
Cell Adhesion Molecules/chemistry/genetics/*metabolism
;
Cell Line
;
Cell Movement
;
Cells, Cultured
;
Culture Techniques
;
Embryo, Nonmammalian
;
Growth Cones/physiology
;
Hepatocyte Growth Factor/metabolism/pharmacology
;
Ligands
;
Nerve Growth Factors/*metabolism/pharmacology
;
Neurons/metabolism
;
Protein Conformation
;
Protein Structure, Tertiary
;
Purinergic P1 Receptor Agonists
;
Purinergic P1 Receptor Antagonists
;
Rats
;
Receptor, Adenosine A2B
;
Receptors, Cell Surface/chemistry/genetics/*metabolism
;
Receptors, Purinergic P1/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Signal Transduction
;
Spinal Cord/cytology/metabolism
;
*Tumor Suppressor Proteins
;
Xanthines/pharmacology
;
Xenopus/embryology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink