Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neuronal activity
The formation of precise synaptic connections in the brain is critically dependent on electric activity, which is important for the elimination of inappropriate connections and for the fine-tuning and stabilization of appropriate ones. The molecular constituents mediating these processes are largely unknown. In an attempt to characterize components by which electric activity influences the development of synapses we have searched for cell surface proteins modulated by neural activity. Up to now we identified two proteins, termed CALEB and CAR, modulated on the surface of neurons by activity-dependent processes.
Our studies revealed that neuronal activity facilitates the prototypical processing of the transmembrane protein CALEB resulting in a membrane associated form with an exposed EGF domain.
To study the role of CALEB in synapse formation a CALEB-deficient mouse was generated. The analysis of synaptic transmission in acute slices of the colliculus superior revealed synapses functionally distinct from wild-type synapses at early but not at mature stages.
CALEB-deficient synapses revealed:
- a reduction of the frequency of spontaneous postsynaptic currents,
- a higher paired-pulse ratio,
- less depression during prolonged repetitive activation,
- and a lower neuritransmitter release probability
at early but not mature postnatal stages.
Our findings indicate that CALEB provides a molecular basis for maintaining normal neurotransmitter release probability at early developmental stages.
Further information:
Jüttner, R., Moré, M.I., Das, D., Babich, A., Meier, J., Henning, M., Erdmann, B., Müller, E.C. Otto,A., Grantyn, R. and Rathjen, F.G. (2005). Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neuronal activity. Neuron 46 (2): 233-245