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Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95

Abstract

CRIPT is a postsynaptic protein that binds selectively to the third PDZ domain (PDZ3) of PSD-95. Here we show that CRIPT also binds directly to microtubules, thereby linking PSD-95 to the microtubule cytoskeleton. Disrupting the CRIPT–PSD-95 interaction in cultured hippocampal neurons with a PDZ3-specific peptide prevented the association of PSD-95 with microtubules and inhibited the synaptic clustering of PSD-95, chapsyn-110/PSD-93 and GKAP (a PSD-95-binding protein). However, the number of synapses and the synaptic clustering of NMDA receptors were unaffected, suggesting that PSD-95-family proteins are not essential for the maintenance of synapses and the synaptic localization of NMDA receptors.

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Figure 1: CRIPT-dependent binding of PSD-95 to microtubules.
Figure 2: CRIPT binds directly to microtubules.
Figure 3: Inhibition of PSD-95 binding to microtubules by Antp-CRIPT peptide.
Figure 4: Inhibition of synaptic clustering of PSD-95 but not of NMDA receptors by Antp-CRIPT.
Figure 5: Quantitation of Antp-CRIPT effects on PSD-95, chapsyn-110, GKAP, CRIPT and NMDA receptor clustering.

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Acknowledgements

M.S. is Assistant Investigator of the Howard Hughes Medical Institute. This work was supported by NIH grant NS35050 to M.S. and by the Armenise-Harvard Foundation (DIBIT-San Raffaele, Italy) to C.S.

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Correspondence to Morgan Sheng.

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Passafaro, M., Sala, C., Niethammer, M. et al. Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95. Nat Neurosci 2, 1063–1069 (1999). https://doi.org/10.1038/15990

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