title: NGF enhances sensory axon growth induced by laminin but not by the L1 cell adhesion molecule.
abstract: Neurotrophins and cell adhesion molecules regulate axon guidance, but their potential coordinate interactions are not well defined. In particular, it has been difficult to define the role of signaling from different surface molecules in neurotrophin-induced axon growth because of the strong dependence of embryonic neurons on this class of molecules for survival. We have addressed this issue using Bax deficient neurons, which do not require neurotrophins for survival. The L1 neural cell adhesion molecule and laminin each supported NGF-independent axon growth of cultured sensory neurons from dorsal root ganglia of embryonic Bax(-/-) mice. However, nerve growth factor (NGF) stimulated additional axon growth of sensory neurons on laminin but not on L1 substrates. Inhibition of the small GTPase RhoA by the dominant-negative mutant RhoA(T19N) restored NGF responsiveness of axon growth on L1 to Bax(-/-) neurons. Constitutively activated RhoA(Q63L) did not affect axon growth on L1 but inhibited NGF-stimulated axon growth on laminin. Consistent with the concept that RhoA was downregulated by NGF in neurons on laminin but not L1, the RhoA inhibitor C2IN-C3 toxin stimulated axon growth on L1 in wild-type DRG neurons in NGF. These results demonstrate a novel substrate-dependent regulation of NGF-induced growth of embryonic sensory axons mediated by RhoA GTPase.
authors.affiliation: Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill 27599-7260, USA.
authors.forename: Rong-Yu
authors.initials: RY
authors.lastname: Liu
authors.forename: Ralf-Steffen
authors.initials: RS
authors.lastname: Schmid
authors.forename: William D
authors.initials: WD
authors.lastname: Snider
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Maness
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D005333:Fetus; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D039841:Leukocyte L1 Antigen Complex; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D020812:Receptor, trkC / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D020742:rhoA GTP-Binding Protein / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D007797:Laminin; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D020932:Nerve Growth Factor; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D020812:Receptor, trkC; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein