Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3
Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3
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DOI：
10.1111/jnc.13353
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发表时间：
2016-01-01
影响因子：
4.7
通讯作者：
Schmeisser, Michael J.
中科院分区：
文献类型：
--
作者：
Dolnik, Anna;Kanwal, Noreen;Schmeisser, Michael J.
Rap GTP酶激活蛋白（RapGAP）是突触功能所必需的，因为它们紧密地调节突触Rap信号传导。在脑中最丰富的突触RapGAP是Spine-associated RapGAP（SPARs）Sipa 1 l1/SPAR和Sipa 1 l2/SPAR 2，而Sipa 1 l3/SPAR 3尚未报道。在这项研究中，我们表明，Sipa 1 l3/SPAR 3是保守的跨物种，有一个独特的表达模式，在发育中的大鼠大脑，并定位于兴奋性突触后。我们进一步证明了Sipa 1 l3/SPAR 3 C-末端是突触后靶向所需的，并代表了Fezzins的相互作用模块，如ProSAPiP 1/Lzts 3，突触后支架蛋白Shank 3的结合伴侣。总之，我们的数据表明，Sipa 1 l3/SPAR 3是一个迄今为止未知的突触RapGAP，这是针对突触后的专业化和相互作用的Fezzins。
Rap GTPase-activating proteins (RapGAPs) are essential for synaptic function as they tightly regulate synaptic Rap signaling. Among the most abundant synaptic RapGAPs in brain are the Spine-associated RapGAPs (SPARs) Sipa1l1/SPAR and Sipa1l2/SPAR2, whereas nothing has been reported on Sipa1l3/SPAR3. In this study, we show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in the developing rat brain and is localized at excitatory postsynapses. We further demonstrate that the Sipa1l3/SPAR3 C-terminus is required for postsynaptic targeting and represents an interaction module for Fezzins such as ProSAPiP1/Lzts3, a binding partner of the postsynaptic scaffold protein Shank3. Taken together, our data imply that Sipa1l3/SPAR3 is a hitherto unknown synaptic RapGAP, which is targeted to postsynaptic specializations and interacts with Fezzins.