Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression.
Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression.
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DOI：
10.1098/rsob.170142
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发表时间：
2017-09
期刊：
影响因子：
5.8
通讯作者：
Fredriksson R
中科院分区：
文献类型：
--
作者：
Perland E;Bagchi S;Klaesson A;Fredriksson R
溶质载体 (SLC) 至关重要，因为它们负责脂质双层分子运输的主要部分。目前已鉴定出430个SLC，其中28个被称为主要促进子超家族（MFS）类型的非典型SLC。它们是 MFSD1、2A、2B、3、4A、4B、5、6、6L、7、8、9、10、11、12、13A、14A 和 14B； SV2A、SV2B 和 SV2C； SVOP 和 SVOPL； SPNS1、SPNS2 和 SPNS3；以及 UNC93A 和 UNC93B1。我们研究了它们的基本特性，我们还包括了 CLN3，一种不属于任何蛋白质家族 (Pfam) 家族的非典型 SLC，因为它与 MFSD8 涉及相同的神经元退行性疾病。通过系统发育分析和生物信息学序列比较，这些蛋白被分为15个家族，称为非典型MFS转运蛋白家族（AMTF1-15）。隐马尔可夫模型用于鉴定从人类到果蝇和秀丽隐杆线虫的直系同源物。拓扑预测揭示了 12 个跨膜片段（除了 CLN3 之外），对应于常见的 MFS 结构。通过单细胞 RNA 测序和脑细胞原位邻近连接分析，鉴定出了几种非典型 SLC 的共表达。最后，在完全氨基酸饥饿后，对下丘脑 N25/2 细胞系中所有基因的转录水平进行了分析，结果显示几种非典型 SLC 的表达水平发生了变化。
Solute carriers (SLCs) are vital as they are responsible for a major part of the molecular transport over lipid bilayers. At present, there are 430 identified SLCs, of which 28 are called atypical SLCs of major facilitator superfamily (MFS) type. These are MFSD1, 2A, 2B, 3, 4A, 4B, 5, 6, 6 L, 7, 8, 9, 10, 11, 12, 13A, 14A and 14B; SV2A, SV2B and SV2C; SVOP and SVOPL; SPNS1, SPNS2 and SPNS3; and UNC93A and UNC93B1. We studied their fundamental properties, and we also included CLN3, an atypical SLC not yet belonging to any protein family (Pfam) clan, because its involvement in the same neuronal degenerative disorders as MFSD8. With phylogenetic analyses and bioinformatic sequence comparisons, the proteins were divided into 15 families, denoted atypical MFS transporter families (AMTF1-15). Hidden Markov models were used to identify orthologues from human to Drosophila melanogaster and Caenorhabditis elegans. Topology predictions revealed 12 transmembrane segments (for all except CLN3), corresponding to the common MFS structure. With single-cell RNA sequencing and in situ proximity ligation assay on brain cells, co-expressions of several atypical SLCs were identified. Finally, the transcription levels of all genes were analysed in the hypothalamic N25/2 cell line after complete amino acid starvation, showing altered expression levels for several atypical SLCs.