Adaptation in the chemotactic guidance of nerve growth cones.
Pathfinding by growing axons in the developing nervous system may be guided by gradients of extracellular guidance factors. Analogous to the process of chemotaxis in microorganisms, we found that axonal growth cones of cultured Xenopus spinal neurons exhibit adaptation during chemotactic migration, undergoing consecutive phases of desensitization and resensitization in the presence of increasing basal concentrations of the guidance factor netrin-1 or brain-derived neurotrophic factor. The desensitization is specific to the guidance factor and is accompanied by a reduction of Ca2+ signalling, whereas resensitization requires activation of mitogen-associated protein kinase and local protein synthesis. Such adaptive behaviour allows the growth cone to re-adjust its sensitivity over a wide range of concentrations of the guidance factor, an essential feature for long-range chemotaxis.
Ming
Guo-li
GL
Division of Biology, University of California at San Diego, La Jolla, California 92093, USA. gming@biomail.ucsd.edu
Wong
Scott T
ST
Henley
John
J
Yuan
Xiao-bing
XB
Song
Hong-jun
HJ
Spitzer
Nicholas C
NC
Poo
Mu-ming
MM
D000220:Adaptation, Biological / Q000187:drug effects; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D002642:Chick Embryo; D004789:Enzyme Activation / Q000187:drug effects; D020439:Growth Cones / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D000075386:Netrin Receptors; D000075388:Netrin-1; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D025521:Tumor Suppressor Proteins; D014981:Xenopus / Q000196:embryology / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D011500:Protein Synthesis Inhibitors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D020928:Mitogen-Activated Protein Kinases