Depolarization and cAMP elevation rapidly recruit TrkB to the plasma membrane of CNS neurons.
Here, we describe a novel mechanism for the rapid regulation of surface levels of the neurotrophin receptor TrkB. Unlike nodose ganglion neurons, both retinal ganglion cells (RGCs) and spinal motor neurons (SMNs) in culture display only low levels of surface TrkB, though high levels are present intracellularly. Within minutes of depolarization or cAMP elevation, surface TrkB levels increase by nearly 4-fold, and this increase is not blocked by cycloheximide. These findings suggest that activity and cAMP elevation rapidly recruit TrkB to the plasma membrane by translocation from intracellular stores. We propose that a fundamental difference between peripheral nervous system (PNS) and central nervous system (CNS) neurons is the activity dependence of CNS neurons for responsiveness to their peptide trophic factors and that differences in membrane compartmentalization of the receptors underlie this difference.
Meyer-Franke
A
A
Stanford University School of Medicine, Department of Neurobiology, California 94305, USA.
Wilkinson
G A
GA
Kruttgen
A
A
Hu
M
M
Munro
E
E
Hanson
M G
MG
Reichardt
L F
LF
Barres
B A
BA
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004594:Electrophysiology; D009046:Motor Neurons / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D000242:Cyclic AMP; D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases