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C‐terminal synaptic targeting elements for postsynaptic density proteins ProSAP1/Shank2 and ProSAP2/Shank3
Author(s) -
Boeckers Tobias M.,
Liedtke Thomas,
Spilker Christina,
Dresbach Thomas,
Bockmann Jürgen,
Kreutz Michael R.,
Gundelfinger Eckart D.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02910.x
Subject(s) - synaptogenesis , postsynaptic density , scaffold protein , postsynaptic potential , biology , microbiology and biotechnology , neuroscience , green fluorescent protein , ankyrin repeat , synapse , inhibitory postsynaptic potential , excitatory postsynaptic potential , signal transduction , receptor , biochemistry , gene
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.