cAMP-dependent growth cone guidance by netrin-1.
Netrin-1 is known to function as a chemoattractant for several classes of developing axons and as a chemorepellent for other classes of axons, apparently dependent on the receptor type expressed by responsive cells. In culture, growth cones of embryonic Xenopus spinal neurons exhibited chemoattractive turning toward the source of netrin-1 but showed chemorepulsive responses in the presence of a competitive analog of cAMP or an inhibitor of protein kinase A. Both attractive and repulsive responses were abolished by depleting extracellular calcium and by adding a blocking antibody against the netrin-1 receptor Deleted in Colorectal Cancer. Thus, nerve growth cones may respond to the same guidance cue with opposite turning behavior, dependent on other coincident signals that set the level of cytosolic cAMP.
Ming
G L
GL
Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Song
H J
HJ
Berninger
B
B
Holt
C E
CE
Tessier-Lavigne
M
M
Poo
M M
MM
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D002645:Chickens; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004625:Embryo, Nonmammalian; D009414:Nerve Growth Factors / Q000494:pharmacology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013116:Spinal Cord / Q000196:embryology*; D013873:Thionucleotides / Q000494:pharmacology; D025521:Tumor Suppressor Proteins; D014981:Xenopus
D000906:Antibodies; D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D013873:Thionucleotides; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; C016957:adenosine-3',5'-cyclic phosphorothioate; D000242:Cyclic AMP