Mutation in the phosphorylation sites of MAP kinase blocks learning-related internalization of apCAM in Aplysia sensory neurons.
The synaptic growth that accompanies 5-HT-induced long-term facilitation of the sensory to motor neuron connection in Aplysia is associated with the internalization of apCAM at the surface membrane of the sensory neuron. We have now used epitope tags to examine the fate of each of the two apCAM isoforms (membrane bound and GPI-linked) and find that only the transmembrane form is internalized. This internalization can be blocked by overexpression of transmembrane constructs with a single point mutation in the two MAPK consensus sites, as well as by injection of a specific MAPK antagonist into sensory neurons. These data suggest MAPK phosphorylation at the membrane is important for the internalization of apCAMs and, thus, may represent an early regulatory step in the growth of new synaptic connections that accompanies long-term facilitation.
Bailey
C H
CH
Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York 10032, USA.
Kaang
B K
BK
Chen
M
M
Martin
K C
KC
Lim
C S
CS
Casadio
A
A
Kandel
E R
ER
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015536:Down-Regulation; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols; D007150:Immunohistochemistry; D007858:Learning / Q000502:physiology*; D048369:MAP Kinase Kinase 1; D008565:Membrane Proteins / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases; D009154:Mutation; D009473:Neuronal Plasticity; D009475:Neurons, Afferent / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D013329:Structure-Activity Relationship
D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D005419:Flavonoids; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D012701:Serotonin; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one