Functional analysis of Drosophila β1,4-N-acetlygalactosaminyltransferases
Functional analysis of Drosophila β1,4-N-acetlygalactosaminyltransferases
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DOI：
10.1093/glycob/cwi017
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发表时间：
2005-04-01
期刊：
影响因子：
4.3
通讯作者：
Irvine, KD
中科院分区：
文献类型：
--
作者：
Haines, N;Irvine, KD
哺乳动物 β 1,4-半乳糖基转移酶家族的成员是研究最深入的糖基转移酶之一，但动物体内对该家族所有成员的需求量此前尚未确定。在这里，我们描述了对两个果蝇基因β 4GalNAcTA (CG8536) 和β 4GalNAcTB (CG14517) 的分析，它们与哺乳动物β 1,4-半乳糖基转移酶同源。与哺乳动物同系物一样，这些糖基转移酶使用 N-乙酰氨基葡萄糖作为受体底物。然而，它们转移的是 N-乙酰半乳糖胺而不是半乳糖。这种活性加上氨基酸序列的相似性，使它们跻身于一组最近鉴定的无脊椎动物 β 1,4-N-乙酰半乳糖氨基转移酶之列。为了研究这些基因的生物学功能，通过不精确切除转座元件（β 4GalNAcTA）或通过基因靶向同源重组（β 4GalNAcTB）产生无效突变。 β 4GalNAcTA 的果蝇突变体具有活力和繁殖力，但表现出的行为表型表明含有糖缀合物的 GalNAc-β 1,4-GlcNAc 在神经元和/或肌肉中具有重要作用。功能。 beta 4GalNAcTB 突变体是可行的，并且没有表现出明显的形态或行为表型。两个基因双突变的果蝇仅表现出与 β4GalNAcTA 突变相关的行为表型。因此，哺乳动物 β4GalT 家族的果蝇同源物对于神经肌肉生理学或发育至关重要，但除此之外并非如此。生存力、生育力或外部形态所需的。
Members of the mammalian beta 1,4-galactosyltransferase family are among the best studied glycosyltransferases, but the requirements for all members of this family within an animal have not previously been determined. Here, we describe analysis of two Drosophila genes, beta 4GalNAcTA (CG8536) and beta 4GalNAcTB (CG14517), that are homologous to mammalian beta 1,4-galactosyltransferases. Like their mammalian homologs, these glycosyltransferases use N-acetylglucosamine as an acceptor substrate. However, they transfer N-acetylgalactosamine rather than galactose. This activity, together with amino acid sequence similarity, places them among a group of recently identified invertebrate beta 1,4-N-acetylgalactosaminyltransferases. To investigate the biological functions of these genes, null mutations were generated by imprecise excision of a transposable element (beta 4GalNAcTA) or by gene-targeted homologous recombination (beta 4GalNAcTB). Flies mutant for beta 4GalNAcTA are viable and fertile but display behavioral phenotypes suggestive of essential roles for GalNAc-beta 1,4-GlcNAc containing glycoconjugates in neuronal and/or muscular. function. beta 4GalNAcTB mutants are viable and display no evident morphological or behavioral phenotypes. Flies doubly mutant for both genes display only the behavioral phenotypes associated with mutation of beta 4GalNAcTA. Thus Drosophila homologs of the mammalian beta 4GalT family are essential for neuromuscular physiology or development but are not otherwise. required for viability, fertility, or external morphology.