突触相关蛋白102的结构、功能及相关研究进展

苏东宁 常丽荣* 武艳*

doi:10.16098/j.issn.0529-1356.2017.05.023

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解剖学报 ›› 2017, Vol. 48 ›› Issue (5) : 628-632. DOI: 10.16098/j.issn.0529-1356.2017.05.023

综述

突触相关蛋白102的结构、功能及相关研究进展

苏东宁¹常丽荣^2* 武艳^2*

作者信息 +

Structure, functions and relative diseases of synapse-associated protein 102

SU Dong-ning¹ CHANG Li-rong^2* WU Yan^2*

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文章历史 +

摘要

突触相关蛋白102（SAP102）是突触后膜区域中一种重要的支架蛋白，属于膜相关鸟苷酸激酶家族（MAGUK），在新生和成熟的神经元中均有高表达。SAP102有助于特化结构域的受体，如N-甲基-D-天冬氨酸（NMDA）受体和α-氨基-3羟基-5甲基-4异恶唑（AMPA）受体和通道蛋白定位在特定膜区域上，并在囊泡内NMDA受体簇的胞质运输过程中起重要的调节作用。此外，SAP102还可参与调节皮质突触的发育。SAP102的表达或功能异常与多种疾病，如阿尔茨海默病与精神分裂症等的发生发展相关。尽管SAP102与神经系统正常生理功能及某些疾病关系密切，但目前人们对SAP102的认识尚不够充分，我们将对SAP102蛋白的结构、生理功能及与之相关疾病的研究进展进行综述。

Abstract

Synapse-associated protein 102 (SAP102) is a significant scaffold protein in postsynaptic density (PSD) and belongs to membraneassociated guanylate kinases (MAGUKs). It is highly expressed in both neonatal and mature neurons. SAP102 plays an important role in the trafficking of NMDA receptor clusters in the vesicles, anchoring certain receptors and channel proteins on the membrane and regulating development of the synapses in the cortex. Abnormal changes of SAP102 are related to many diseases, such as Alzheimer’s disease and schizophrenia. Although it is crucial for both the normal biology functions of nervous system and the occurrence or development of certain diseases，the study of SAP102 is not enough. In this review, we focus on the structure, functions and relative diseases of SAP102.

关键词

Key words

Synapse associated protein 102 / Membrane associated guanylate kinases / N methyl D aspartate receptor / Postsynaptic density

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苏东宁常丽荣武艳. 突触相关蛋白102的结构、功能及相关研究进展[J]. 解剖学报. 2017, 48(5): 628-632 https://doi.org/10.16098/j.issn.0529-1356.2017.05.023

SU Dong-ning CHANG Li-rong WU Yan. Structure, functions and relative diseases of synapse-associated protein 102[J]. Acta Anatomica Sinica. 2017, 48(5): 628-632 https://doi.org/10.16098/j.issn.0529-1356.2017.05.023

参考文献

［1］Müller BM, Kistner U, Kindler S, et al. SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo［J］. Neuron, 1996, 17(2): 255-265.

［2］Fujita A, Kurachi Y. SAP family proteins［J］. Biochem Biophys Res Commun, 2000, 269(1): 1-6.

［3］Zheng CY, Petralia RS, Wang YX, et al. SAP102 is a highly mobile MAGUK in spines［J］. J Neurosci, 2010, 30(13): 4757-4766.

［4］Chen BS, Thomas EV, SanzClemente A, et al. NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants［J］. J Neurosci, 2011, 31(1): 89-96.

［5］Wei Z, Behrman B, Wu WH, et al. Subunit-specific regulation of N-methyl-d-aspartate (NMDA) receptor trafficking by SAP102 protein splice variants［J］. J Biol Chem, 2015, 290(8): 5105-5116.

［6］Bustos FJ, Varela-Nallar L, Campos M, et al. PSD95 suppresses dendritic arbor development in mature hippocampal neurons by occluding the clustering of NR2B-NMDA receptors［J］. PLoS One, 2014, 9(4): e94037.

［7］Murata Y, Constantine-Paton M. Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway［J］. J Neurosci, 2013, 33(11): 5040-5052.

［8］Sans N, Petralia RS, Wang YX, et al. A developmental change in NMDA receptor-associated proteins at hippocampal synapses［J］. J Neurosci, 2000, 20(3): 1260-1271.

［9］Matsunaga Y, Negishi T, Hatakeyama A, et al. Impairment of synaptic development in the hippocampus of diabetic Goto-Kakizaki rats［J］. Int J Dev Neurosci, 2016, 53: 58-67.

［10］Proctor DT, Coulson EJ, Dodd PR. Reduction in post-synaptic scaffolding PSD-95 and SAP-102 protein levels in the Alzheimer inferior temporal cortex is correlated with disease pathology［J］. J Alzheimers Dis, 2010, 21(3): 795-811.

［11］Farzana F, Zalm R, Chen N, et al. Neurobeachin regulates glutamate- and GABA-receptor targeting to synapses via distinct pathways［J］. Mol Neurobiol, 2016, 53(4):2112-2123.

［12］van Zundert B, Yoshii A, Constantine-Paton M. Receptor compartmentalization and trafficking at glutamate synapses: a developmental proposal［J］. Trends Neurosci, 2004, 27(7): 428-437.

［13］Chen BS, Gray JA, Sanz-Clemente A, et al. SAP102 mediates synaptic clearance of NMDA receptors［J］. Cell Rep, 2012, 2(5): 1120-1128.

［14］Sans N, Wang PY, Du Q, et al. mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression［J］. Nat Cell Biol, 2005, 7(12): 1179-1190.

［15］Washbourne P, Liu XB, Jones EG, et al. Cycling of NMDA receptors during trafficking in neurons before synapse formation［J］. J Neurosci, 2004, 24(38): 8253-8264.

［16］Elias GM, Apostolides PF, Kriegstein AR, et al. Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development［J］. Proc Natl Acad Sci, 2008, 105(52): 20953-20958.

［17］Lauks J, Klemmer P, Farzana F, et al. Synapse associated protein 102 (SAP102) binds the C-terminal part of the scaffolding protein neurobeachin［J］. PLoS One, 2012, 7(6): e39420.

［18］Davey F, Hill M, Falk J, et al. Synapse associated protein 102 is a novel binding partner to the cytoplasmic terminus of neurone-glial related cell adhesion molecule［J］. J Neurochem, 2005, 94(5): 1243-1253.

［19］Thurner P, Gsandtner I, Kudlacek O, et al. A two-state model for the diffusion of the a2a adenosine receptor in hippocampal neurons agonist-induced switch to slow mobility is modified by synapse-associated protein 102 (sap102)［J］. J Biol Chem, 2014, 289(13): 9263-9274.

［20］Bécamel C, Gavarini S, Chanrion B, et al. The serotonin 5-HT2A and 5-HT2C receptors interact with specific sets of PDZ proteins［J］. J Biol Chem, 2004, 279(19): 20257-20266.

［21］Zanni G, Van Esch H, Bensalem A, et al. A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation［J］. Neurogenetics, 2010, 11(2): 251-255.

［22］Kumar R, Ha T, Pham D, et al. A non-coding variant in the 5’UTR of DLG3 attenuates protein translation to cause non-syndromic intellectual disability［J］. Eur J Hum Genet, 2016, 24(11):1612-1616.

［23］Crocker-Buque A, Currie SP, Luz LL, et al. Altered thalamocortical development in the SAP102 knockout model of intellectual disability［J］. Hum Mol Genet, 2016, 25(18):4052-4061.

［24］Kristiansen LV, Beneyto M, Haroutunian V, et al. Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia［J］. Mol Psychiatry, 2006, 11(8): 737-747.

［25］Clinton SM, Haroutunian V, Meador-Woodruff JH. Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia［J］. J Neurochem, 2006, 98(4): 1114-1125.

［26］Meador-Woodruff JH, Clinton SM, Beneyto M, et al. Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia［J］. Ann NY Acad Sci, 2003, 1003(1): 75-93.

［27］Zhang Y, Li P, Feng J, et al. Dysfunction of NMDA receptors in Alzheimer’s disease［J］. Neurol Sci, 2016: 37(7):1039-1047.

［28］Fan J, Cowan CM, Zhang LYJ, et al. Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington's disease［J］. J Neurosci, 2009, 29(35): 10928-10938.

［29］Ricobaraza A, Cuadrado-Tejedor M, Marco S, et al. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease［J］. Hippocampus, 2012, 22(5): 1040-1050.