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Publication : Role of the internal Shank-binding segment of glutamate receptor delta2 in synaptic localization and cerebellar functions.

First Author  Yasumura M Year  2008
Journal  Neurosci Lett Volume  433
Issue  2 Pages  146-51
PubMed ID  18249497 Mgi Jnum  J:150621
Mgi Id  MGI:3851080 Doi  10.1016/j.neulet.2008.01.009
Citation  Yasumura M, et al. (2008) Role of the internal Shank-binding segment of glutamate receptor delta2 in synaptic localization and cerebellar functions. Neurosci Lett 433(2):146-51
abstractText  Glutamate receptor (GluR) delta2 selectively expressed in cerebellar Purkinje cells (PCs) plays key roles in cerebellar long-term depression (LTD), motor learning and formation of parallel fiber (PF)-PC synapses. We have recently shown that the PDZ [postsynaptic density (PSD)-95/Discs large/zona occludens-1]-binding domain at the C-terminal, the T site, is essential for LTD induction and the regulation of climbing fiber (CF) territory, but is dispensable for synaptic localization of GluRdelta2, PF-PC synapse formation and CF elimination process. To investigate the functional roles of the S segment, the second PDZ-binding domain in the middle of the C-terminal cytoplasmic region, we generated GluRdelta2DeltaS mice carrying mutant GluRdelta2 lacking this segment. The amount of GluRdelta2DeltaS in mutant mice was reduced compared with that of GluRdelta2 in wild-type mice. However, the extent of decrease was much larger in the PSD fractions than in cerebellar homogenates, suggesting the requirement of the S segment for efficient synaptic localization. Furthermore, mismatched PF synapses and free spines emerged and CF-innervation territory on PC dendrites expanded in GluRdelta2DeltaS mice. On the other hand, the performance in the rotarod test was comparable between wild-type and GluRdelta2DeltaS mice. These results suggest that the S segment and T site, the two PDZ-binding domains in the C-terminal cytoplasmic region, are differentially involved in diverse GluRdelta2 functions.
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