Endocytosis-dependent desensitization and protein synthesis-dependent resensitization in retinal growth cone adaptation.
It has been proposed that growth cones navigating through gradients adapt to baseline concentrations of guidance cues. This adaptation process is poorly understood. Using the collapse assay, we show that adaptation in Xenopus laevis retinal growth cones to the guidance cues Sema3A or netrin-1 involves two processes: a fast, ligand-specific desensitization that occurs within 2 min of exposure and is dependent on endocytosis, and a slower, ligand-specific resensitization, which occurs within 5 min and is dependent upon protein synthesis. These two phases of adaptation allow retinal axons to adjust their range of sensitivity to specific guidance cues.
Piper
Michael
M
Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, United Kingdom.
Salih
Saif
S
Weinl
Christine
C
Holt
Christine E
CE
Harris
William A
WA
D000220:Adaptation, Biological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology; D019556:COS Cells / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique / Q000379:methods; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000502:physiology*; D000075388:Netrin-1; D009474:Neurons / Q000166:cytology*; D039942:Neuropilin-1 / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012160:Retina / Q000166:cytology; D040121:Semaphorin-3A / Q000502:physiology*; D018709:Statistics, Nonparametric; D013997:Time Factors; D014162:Transfection / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014982:Xenopus laevis
D001152:Arsenicals; D015815:Cell Adhesion Molecules; D054422:Chemokine CCL22; D019742:Chemokines, CC; D009414:Nerve Growth Factors; D011500:Protein Synthesis Inhibitors; D040121:Semaphorin-3A; D025521:Tumor Suppressor Proteins; C029341:oxophenylarsine; D039942:Neuropilin-1; D000075388:Netrin-1; D000841:Anisomycin; D003513:Cycloheximide