LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity
LASS3 (longevity assurance homologue 3) is a mainly testis-specific (dihydro)ceramide synthase with relatively broad substrate specificity
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DOI：
10.1042/bj20060379
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发表时间：
2006-09-15
影响因子：
4.1
通讯作者：
Igarashi, Yasuyuki
中科院分区：
文献类型：
--
作者：
Mizutani, Yukiko;Kihara, Akio;Igarashi, Yasuyuki
LASS（长寿保证同系物）家族成员从酵母到哺乳动物都高度保守。已经鉴定并表征了5个小鼠和人类的LASS家族成员，即LASS 1、LASS2、LASS4、LASS5和LASS6。在本研究中，我们克隆了两个迄今尚未鉴定的小鼠LASS3 cDNA转录变体，它们编码一个384个氨基酸的蛋白（LASS3）和一个419个氨基酸的蛋白（LASS3-long）。在体内，[H-3]二氢鞘氨醇标记和电喷雾电离质谱显示，LASS3亚型的过量产生导致几种神经酰胺种类的增加，其中一些倾向于具有中至长链脂肪酰基辅酶a的神经酰胺种类。在体外（二氢）神经酰胺合成酶实验中也观察到类似的底物偏好。这些结果表明LASS3具有（二氢）神经酰胺合成活性，并且具有相对广泛的底物特异性。我们还发现，除了在皮肤中表现较弱外，LASS3 mRNA的表达几乎仅限于睾丸，这意味着LASS3在该腺体中发挥重要作用。
The LASS (longevity assurance homologue) family members are highly conserved from yeasts to mammals. Five mouse and human LASS family members, namely LASS 1, LASS2, LASS4, LASS5 and LASS6, have been identified and characterized. In the present study we cloned two transcriptional variants of hitherto-uncharacterized mouse LASS3 cDNA, which encode a 384-amino-acid protein (LASS3) and a 419-amino-acid protein (LASS3-long). In vivo, [H-3]dihydrosphingosine labelling and electrospray-ionization MS revealed that overproduction of either LASS3 isoform results in increases in several ceramide species, with some preference toward those having middle- to long-chain-fatty acyl-CoAs. A similar substrate preference was observed in an in vitro (dihydro)ceramide synthase assay. These results indicate that LASS3 possesses (dihydro)ceramide synthesis activity with relatively broad substrate specificity. We also found that, except for a weak display in skin, LASS3 mRNA expression is limited almost solely to testis, implying that LASS3 plays an important role in this gland.