Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neuronal activity.
In an attempt to characterize the molecular components by which electric activity influences the development of synapses, we searched for cell surface proteins modulated by calcium influx and glutamate receptor activity. Here, we report that neuronal depolarization facilitates the conversion of CALEB, which results in a truncated transmembrane form with an exposed EGF domain. To characterize the role of CALEB in synapse development, synaptic features were investigated in slices of the colliculus superior from CALEB-deficient mice. In the absence of CALEB, the number of synapses and their morphological characteristics remained unchanged. However, in CALEB-deficient mice, synapses displayed higher paired-pulse ratios, less depression during prolonged repetitive activation, a lower rate of spontaneous postsynaptic currents, and a lower release probability at early but not mature postnatal stages. Our findings indicate that CALEB provides a molecular basis for maintaining normal release probability at early developmental stages.
Jüttner
René
R
Max-Delbrück-Centrum, Robert-Rössle-Strasse 10, 13092 Berlin, Germany.
Moré
Margret I
MI
Das
Debashish
D
Babich
Aleksei
A
Meier
Jochen
J
Henning
Mechthild
M
Erdmann
Bettina
B
Mu Ller
Eva-Christiana
EC
Otto
Albrecht
A
Grantyn
Rosemarie
R
Rathjen
Fritz G
FG
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002642:Chick Embryo; D004815:Epidermal Growth Factor / Q000172:deficiency*; D019706:Excitatory Postsynaptic Potentials; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D009924:Organ Culture Techniques; D013477:Superior Colliculi / Q000254:growth & development; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D004815:Epidermal Growth Factor