Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95.
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.
Passafaro
M
M
Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, HHMI/Wellman 423, 50 Blossom Street, Boston, Massachusetts 02114, USA.
Sala
C
C
Niethammer
M
M
Sheng
M
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000074407:SAP90-PSD95 Associated Proteins; D013569:Synapses / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; D000074407:SAP90-PSD95 Associated Proteins; D016708:Synaptophysin; C033652:postsynaptic density proteins; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases