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THOMAS BIEDERER

Synapse Formation in the Central Nervous System
The development of synapses is necessary to establish a functional nervous system. Neurons form new synapses both during early development and in the adult brain. This process allows information to be transmitted from the pre- to the postsynaptic cell. Our studies aim to address on the molecular level how synaptic specializations are assembled at distinct plasma membrane sites from a limited number of components. Our goal is to identify and characterize the events that initiate synapse formation and the steps that lead to its completion.

Characterization of Synaptic Cell Adhesion Molecules
Synaptic cell adhesion molecules mediate the physical contact between pre- and postsynaptic neurons. During synaptogenesis, these trans-synaptic interactions align and demarcate the membrane surfaces of the pre- and postsynaptic neuron. Subsequently, membrane specializations are formed on both sides of the synapse: The presynaptic terminal holds synaptic vesicles that are ready for release, and the postsynaptic membrane contains the matching neurotransmitter receptors.

We focus on the molecular characterization of the SynCAM (Synaptic Cell Adhesion Molecule) family of proteins in synapse formation. SynCAM proteins are adhesion molecules of the immunoglobulin superfamily with three extracellular immunoglobulin-like domains and a single transmembrane domain. SynCAM 1 triggers synapse formation and promotes neurotransmission through its trans-synaptic interactions. SynCAM 1 and the other family members are expressed in all brain regions during synaptogenesis, indicating a general role in this process.

Our group employs multiple approaches to characterize synapse formation. We utilize biochemical and molecular biological methods to investigate the molecular environment of synaptic cell adhesion molecules. These molecular studies are complemented by functional analyses of neuronal cultures employing optical imaging techniques. Finally, in vivo studies of mouse models allow for analysis of synapse formation in the developing brain.

Significance
Synapse formation and modulation are likely to play central roles in learning and memory. Importantly, synaptic dysfunctions occur in human illnesses like mental retardation and Alzheimer's disease. Molecular insight into synaptogenesis in the healthy brain will allow development of approaches to improve or treat these human neurodevelopmental and neurodegenerative disorders.

Selected Publications
Biederer, T., Sara, Y., Mozhayeva, M., Atasoy, D., Liu, X., Kavalali, E.T. and Südhof, T.C. SynCAM, a synaptic adhesion molecule that drives synapse assembly. Science 297, 1525-1531 (2002)

Sara, Y., Biederer, T., Atasoy, D., Chubykin, A., Mozhayeva, M.G., Südhof, T.C. and Kavalali, E.T. Selective capability of SynCAM and neuroligin for functional synapse assembly. J. Neuroscience 25, 260-270 (2005)

Biederer, T. Progress from the postsynaptic side: signaling in synaptic differentiation. Science STKE 274, pe9 (review) (2005)

Akins, M. and Biederer, T. Cell-cell interactions in synaptogenesis. Current Opinion in Neurobiology 16, 83-89 (review) (2006)

Biederer, T. Bioinformatic characterization of the SynCAM family of immunoglobulin-like domain containing adhesion molecules. Genomics 87, 139-150 (2006)

Last Updated 12-18-06