Tetraspanin (TSPAN) protein family forms a family of transmembrane proteins that act as organizers/scaffold for other proteins. TSPANs are primarily present on plasma membranes although they are also found in other biological membranes. They are organized in tetraspanin-enriched microdomains (TEMs), which allow spatiotemporal tuning of protein functions through the control of their membrane localization. TSPAN6 and TSPAN7 are close paralogs expressed in different tissues, TSPAN7 being highly expressed in the brain. Their functions only started to be unveiled in the late 2000’s and are still poorly understood. Here, we introduce how TSPAN7 was first highlighted has a protein mutated in some forms of X-linked mental retardation, which was later proposed to be caused by defects in neuronal morphogenesis and synaptic transmission. We then discuss the impacts TSPAN7 has on cell morphology of dendritic cells and osteoclasts, through rearrangement of actin cytoskeleton and how TSPAN7 was shown to be a target of autoantibody in patients suffering from type 1 diabetes. Finally, we are addressing the double edge sword that is TSPAN7 in cancer. In the second part of this review, we address the known roles of TSPAN6 and how this protein was shown to participate in synaptic transmission and in amyloid precursor protein secretion, which may contribute to Alzheimer’s disease pathology. We conclude this review by discussing the anti-inflammatory effect of TSPAN6.

中文翻译：

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四跨膜蛋白 7 及其最接近的旁系同源四跨膜蛋白 6：膜组织者，在大脑发育、病毒感染、先天免疫、糖尿病和癌症中具有关键功能。

四跨膜蛋白 (TSPAN) 蛋白家族形成跨膜蛋白家族，充当其他蛋白的组织者/支架。TSPAN 主要存在于质膜上，但也存在于其他生物膜中。它们被组织成富含四跨膜蛋白的微域（TEM），从而可以通过控制其膜定位来对蛋白质功能进行时空调节。TSPAN6 和 TSPAN7 是在不同组织中表达的密切旁系同源物，其中 TSPAN7 在大脑中高度表达。它们的功能直到 2000 年代末才开始被揭开，而且人们对它们的了解仍然很少。在这里，我们介绍了 TSPAN7 最初是如何在某些形式的 X 连锁智力障碍中发现蛋白质突变的，后来提出这种突变是由神经元形态发生和突触传递缺陷引起的。然后我们讨论了 TSPAN7 通过肌动蛋白细胞骨架的重排对树突状细胞和破骨细胞的细胞形态的影响，以及 TSPAN7 如何被证明是 1 型糖尿病患者自身抗体的靶标。最后，我们正在讨论癌症中的 TSPAN7 这把双刃剑。在本综述的第二部分中，我们讨论了 TSPAN6 的已知作用，以及该蛋白如何参与突触传递和淀粉样前体蛋白分泌，这可能有助于阿尔茨海默病的病理学。我们通过讨论 TSPAN6 的抗炎作用来结束本综述。