2022
DOI: 10.1093/cercor/bhac123
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Sapap4deficiency leads to postsynaptic defects and abnormal behaviors relevant to hyperkinetic neuropsychiatric disorder in mice

Abstract: Postsynaptic proteins play critical roles in synaptic development, function, and plasticity. Dysfunction of postsynaptic proteins is strongly linked to neurodevelopmental and psychiatric disorders. SAP90/PSD95-associated protein 4 (SAPAP4; also known as DLGAP4) is a key component of the PSD95–SAPAP–SHANK excitatory postsynaptic scaffolding complex, which plays important roles at synapses. However, the exact function of the SAPAP4 protein in the brain is poorly understood. Here, we report that Sapap4 knockout (… Show more

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Cited by 3 publications
(11 citation statements)
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“…The ubiquitination and degradation of SAPAPs at synapses is thought to be required for the normal activity-dependent remodeling of postsynaptic scaffold proteins such as PSD-95 and SHANKs, as well as excitatory synaptic scaling [ 86 ]. Consistent with the role of SAPAPs in synaptic scaling, deletion or perturbation of different SAPAP family members in mice also leads to alterations in the PSD levels of receptors and scaffold proteins, including NMDARs, AMPARs, mGluRs, Homer, SHANK, and αCaMKII [ 13 , 14 , 15 , 16 , 17 , 99 ]. Strikingly, not only the deletion of the repeat region R1 in SAPAP [ 86 ], but also the removal of SHANK [ 100 ], leads to the loss of AMPAR-containing synapses, along with impaired synaptic transmission.…”
Section: Roles Of Sapaps In Synaptic Structure and Functionmentioning
confidence: 86%
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“…The ubiquitination and degradation of SAPAPs at synapses is thought to be required for the normal activity-dependent remodeling of postsynaptic scaffold proteins such as PSD-95 and SHANKs, as well as excitatory synaptic scaling [ 86 ]. Consistent with the role of SAPAPs in synaptic scaling, deletion or perturbation of different SAPAP family members in mice also leads to alterations in the PSD levels of receptors and scaffold proteins, including NMDARs, AMPARs, mGluRs, Homer, SHANK, and αCaMKII [ 13 , 14 , 15 , 16 , 17 , 99 ]. Strikingly, not only the deletion of the repeat region R1 in SAPAP [ 86 ], but also the removal of SHANK [ 100 ], leads to the loss of AMPAR-containing synapses, along with impaired synaptic transmission.…”
Section: Roles Of Sapaps In Synaptic Structure and Functionmentioning
confidence: 86%
“…Additionally, Sapap4 mRNA shows high expression in layer 5 of the cortex. In addition to these areas, Sapap4 is also strongly expressed in the adult rodent thalamus [ 17 , 18 ] and striatum [ 13 , 82 ]—second only to Sapap3 . Of particular interest, Sapap4 mRNA is strongly expressed in the locus coeruleus [ 18 ] as well as the ventricular zone and migrating neurons [ 34 ].…”
Section: Sapap Familymentioning
confidence: 99%
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