CNR Institute of Neuroscience, Department of Medical Pharmacology, University of Milan, Milan 20129, Italy.
Neuron. 2012 Mar 22;73(6):1143-58. doi: 10.1016/j.neuron.2012.01.021. Epub 2012 Mar 21.
Mutations in TSPAN7--a member of the tetraspanin protein superfamily--are implicated in some forms of X-linked intellectual disability. Here we show that TSPAN7 overexpression promotes the formation of filopodia and dendritic spines in cultured hippocampal neurons from embryonic rats, whereas TSPAN7 silencing reduces head size and stability of spines and AMPA receptor currents. Via its C terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking. These findings indicate that, in hippocampal neurons, TSPAN7 regulates AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability.
TSPAN7 突变——四跨膜蛋白超家族的一个成员——与一些形式的 X 连锁智力障碍有关。在这里，我们表明 TSPAN7 的过表达促进了培养的来自胚胎大鼠海马神经元的丝状伪足和树突棘的形成，而 TSPAN7 的沉默减少了头部大小和棘的稳定性以及 AMPA 受体电流。通过其 C 端，TSPAN7 与蛋白相互作用激酶 1（PICK1）的 PDZ 结构域相互作用，以调节 PICK1 和 GluR2/3 相关和 AMPA 受体转运。这些发现表明，在海马神经元中，TSPAN7 通过限制 PICK1 对 AMPA 受体的可及性来调节 AMPA 受体转运，并提出了一种谷氨酸能突触功能成熟的附加机制，其损伤与智力障碍有关。
