N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism.
N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism.
复制标题
N-乙基马来酰亚胺敏感因子与5-羟色胺转运蛋白相互作用并调节其运输：自闭症中对病理生理学的影响。
DOI：
10.1186/2040-2392-5-33
复制
发表时间：
2014
期刊：
影响因子：
6.2
通讯作者：
Mori N
中科院分区：
文献类型：
--
作者：
Iwata K;Matsuzaki H;Tachibana T;Ohno K;Yoshimura S;Takamura H;Yamada K;Matsuzaki S;Nakamura K;Tsuchiya KJ;Matsumoto K;Tsujii M;Sugiyama T;Katayama T;Mori N
5-羟色胺转运体（SERT）功能的变化与自闭症有关。SERT功能受存在于细胞表面的转运蛋白分子数量的影响，其受各种细胞机制的调节，包括与其他蛋白质的相互作用。因此，我们寻找新的SERT结合蛋白，并调查是否有这样的蛋白质的表达在自闭症受试者的影响。新的SERT结合蛋白的下拉系统进行了检查。在HEK 293-hSERT细胞中研究了敲低新型SERT结合蛋白后SERT功能和膜表达的改变。在小鼠脑中评价SERT与蛋白质的内源性相互作用。将自闭症患者死后大脑和淋巴细胞中SERT（SLC 6A 4）和SERT结合蛋白mRNA表达的变化与非临床对照进行比较。N-乙基马来酰亚胺敏感因子（NSF）是一种新的SERT结合蛋白。NSF与SERT共定位于质膜，并且NSF敲低导致SERT在细胞膜上的表达降低和SERT摄取功能降低。NSF与SERT内源性共定位，并与SERT相互作用。虽然SLC 6A 4的表达没有显著变化，但NSF的表达在死后大脑中倾向于减少，并且在自闭症受试者的淋巴细胞中显著减少，这与临床症状的严重程度相关。这些数据清楚地表明，NSF在生理条件下与SERT相互作用，并且是SERT膜运输和摄取功能所需的。一个可能的作用，NSF在自闭症的病理生理学通过调制SERT贩运，建议。
Changes in serotonin transporter (SERT) function have been implicated in autism. SERT function is influenced by the number of transporter molecules present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. Thus, we searched for novel SERT-binding proteins and investigated whether the expression of one such protein was affected in subjects with autism. Novel SERT-binding proteins were examined by a pull-down system. Alterations of SERT function and membrane expression upon knockdown of the novel SERT-binding protein were studied in HEK293-hSERT cells. Endogenous interaction of SERT with the protein was evaluated in mouse brains. Alterations in the mRNA expression of SERT (SLC6A4) and the SERT-binding protein in the post-mortem brains and the lymphocytes of autism patients were compared to nonclinical controls. N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF was co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and decreased SERT uptake function. NSF was endogenously co-localized with SERT and interacted with SERT. While SLC6A4 expression was not significantly changed, NSF expression tended to be reduced in post-mortem brains, and was significantly reduced in lymphocytes of autistic subjects, which correlated with the severity of the clinical symptoms. These data clearly show that NSF interacts with SERT under physiological conditions and is required for SERT membrane trafficking and uptake function. A possible role for NSF in the pathophysiology of autism through modulation of SERT trafficking, is suggested.
登录
查看更多内容
影响因子：
4.7
作者：
Azmitia, Efrain C.;Singh, Jorawer S.;Whitaker-Azmitia, Patricia M.
通讯作者：
Whitaker-Azmitia, Patricia M.
影响因子：
4.4
作者：
Cupello, A;Favale, E;Albano, C
通讯作者：
Albano, C
影响因子：
3
作者：
Czesak, Margaret;Bums, Ariel M.;Albert, Paul R.
通讯作者：
Albert, Paul R.
影响因子：
7.6
作者：
Cross, Sarah;Kim, Soo-Jeong;Veenstra-VanderWeele, Jeremy
通讯作者：
Veenstra-VanderWeele, Jeremy
影响因子：
3.9
作者：
COOK, EH;LEVENTHAL, BL;FREEDMAN, DX
通讯作者：
FREEDMAN, DX