These authors contributed equally to the work
C-terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3
Article first published online: 23 DEC 2004
Journal of Neurochemistry
Volume 92, Issue 3, pages 519–524, February 2005
How to Cite
Boeckers, T. M., Liedtke, T., Spilker, C., Dresbach, T., Bockmann, J., Kreutz, M. R. and Gundelfinger, E. D. (2005), C-terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3. Journal of Neurochemistry, 92: 519–524. doi: 10.1111/j.1471-4159.2004.02910.x
- Issue published online: 23 DEC 2004
- Article first published online: 23 DEC 2004
- Received December 11, 2003; revised manuscript received September 20, 2004; accepted September 21, 2004.
- adaptor protein;
- chemical synapse;
- postsynaptic density;
- sterile alpha motif;
- synapse assembly
Synapses are specialized contact sites mediating communication between neurons. Synaptogenesis requires the specific assembly of protein clusters at both sides of the synaptic contact by mechanisms that are barely understood. We studied the synaptic targeting of multi-domain proteins of the ProSAP/Shank family thought to serve as master scaffolding molecules of the postsynaptic density. In contrast to Shank1, expression of green-fluorescent protein (GFP)-tagged ProSAP1/Shank2 and ProSAP2/Shank3 deletion constructs in hippocampal neurons revealed that their postsynaptic localization relies on the integrity of the C-termini. The shortest construct that was perfectly targeted to synaptic sites included the last 417 amino acids of ProSAP1/Shank2 and included the C-terminal sterile alpha motif (SAM) domain. Removal of 54 residues from the N-terminus of this construct resulted in a diffuse distribution in the cytoplasm. Altogether, our data delineate a hitherto unknown targeting signal in both ProSAP1/Shank2 and ProSAP2/Shank3 and provide evidence for an implication of these proteins and their close homologue, Shank1, in distinct molecular pathways.