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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function.
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DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function.

机译：DLGS97 / SAP97在发育上被上调，是复杂的成人行为以及突触形态和功能所必需的。

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The synaptic membrane-associated guanylate kinase (MAGUK) scaffolding protein family is thought to play key roles in synapse assembly and synaptic plasticity. Evidence supporting these roles in vivo is scarce, as a consequence of gene redundancy in mammals. The genome of Drosophila contains only one MAGUK gene, discs large (dlg), from which two major proteins originate: DLGA [PSD95 (postsynaptic density 95)-like] and DLGS97 [SAP97 (synapse-associated protein)-like]. These differ only by the inclusion in DLGS97 of an L27 domain, important for the formation of supramolecular assemblies. Known dlg mutations affect both forms and are lethal at larval stages attributable to tumoral overgrowth of epithelia. We generated independent null mutations for each, dlgA and dlgS97. These allowed unveiling of a shift in expression during the development of the nervous system: predominant expression of DLGA in the embryo, balanced expression of both during larval stages, and almost exclusive DLGS97 expression in the adult brain. Loss of embryonic DLGS97 does not alter the development of the nervous system. At larval stages, DLGA and DLGS97 fulfill both unique and partially redundant functions in the neuromuscular junction. Contrary to dlg and dlgA mutants, dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship, whereas simpler behaviors like locomotion and odor and light perception are spared. We propose that the increased repertoire of associations of a synaptic scaffold protein given by an additional domain of protein-protein interaction underlies its ability to integrate molecular networks required for complex functions in adult synapses.
机译：突触膜相关的鸟苷酸激酶（MAGUK）支架蛋白家族被认为在突触组装和突触可塑性中起关键作用。由于哺乳动物中基因冗余，缺乏在体内支持这些作用的证据。果蝇的基因组仅包含一个MAGUK基因，盘状大（dlg），起源于两种主要蛋白质：DLGA [PSD95（突触后密度95）样]和DLGS97 [SAP97（突触相关蛋白）样]。这些仅在DLGS97中包含一个L27结构域而有所不同，这对于形成超分子组装非常重要。已知的dlg突变会影响这两种形式，并在幼虫阶段致死，这是由于上皮的肿瘤过度生长所致。我们为dlgA和dlgS97分别生成了独立的无效突变。这些可以揭示神经系统发育过程中表达的变化：DLGA在胚胎中的主要表达，幼虫阶段的平衡表达以及成年大脑中几乎排他的DLGS97表达。丢失DLGS97胚胎不会改变神经系统的发育。在幼体阶段，DLGA和DLGS97在神经肌肉接头中既履行独特的职能，又履行部分冗余的职能。与dlg和dlgA突变体相反，dlgS97突变体可以成年，但它们在复杂的行为（如趋光性，昼夜节律活动和求爱）中表现出明显的变化，而诸如运动，气味和光线感知等简单行为却可以幸免。我们提出，由蛋白质-蛋白质相互作用的额外域赋予的突触支架蛋白缔合的库增加，是其整合成人突触中复杂功能所需的分子网络的能力的基础。

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