| Abstract No.: | B-B2048 |
| Country: | Canada |
| | |
| Title: | DEVELOPMENTAL REGULATION OF SYNAPSE ELIMINATION BY SEMAPHORIN 5B. |
| | |
| Authors/Affiliations: | 1 Lucia Tapia*; 1 Katie Cockburn; 1 Wenyan Wang; 1 Erin Currie; 1 Timothy P. O'Connor; 1 Shernaz X. Bamji;
1 University of British Columbia, Vancouver, BC, Canada
|
| | |
| Content: | During the development of the nervous system, environmental cues guide
growing axons to targets where neuronal contacts are created through the formation of synapses. Excess axonal branches and synaptic contacts are often formed during development, and are pruned or eliminated at later stages to create specific neuronal connections. The semaphorin family of proteins is well known for its role as guidance cues, and more recent evidence also suggests a role for these proteins in synapse elimination. Here we demonstrate that semaphorin 5B (Sema5B) is expressed in the developing and adult hippocampus and localizes to a subset of synapses in cultured hippocampal neurons. Sema5B is proteolytically processed in the developing and adult brain. Similar processing occurs in hippocampal neurons in vitro resulting in a secreted fragment containing the sema domain being released by hippocampal cells. Overexpression of full-length Sema5B or bath application of a secreted fragment containing the semaphorin domain
of Sema5B, results in a rapid pruning of synaptic connections. The
semaphorin domain is necessary for synapse elimination as overexpression of Sema5B lacking this domain results in wildtype number of synapses. In addition, knockdown of endogenous Sema5B results in an increase in synaptic number and size. These results suggests that synapse elimination may by differentially regulated by Sema5B in developing and adult mice.
|
| | |
| Back |
|
