Chondroitin / dermatan sulfate modification enzymes in zebrafish development.
Chondroitin / dermatan sulfate modification enzymes in zebrafish development.
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DOI：
10.1371/journal.pone.0121957
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ledin J
中科院分区：
文献类型：
--
作者：
Habicher J;Haitina T;Eriksson I;Holmborn K;Dierker T;Ahlberg PE;Ledin J
软骨素/硫酸皮肤素（CS/DS）蛋白聚糖由连接至特定蛋白质上的丝氨酸残基的重复GalNAc-GlcA/IdoA二糖单元的无分支硫酸化多糖链组成。CS/DS蛋白聚糖在细胞外基质中含量丰富，在组织发育和体内平衡中具有重要功能。在这份报告中，脊椎动物基因编码的酶，修改CS/DS的系统发育分析。我们在斑马鱼基因组中鉴定了磺基转移酶chst 7，chst 11，chst 13，chst 14，chst 15和ust以及差向异构酶dse的单直链基因。相比之下，发现哺乳动物磺基转移酶CHST 3和CHST 12以及差向异构酶DSEL有两个拷贝，分别命名为chst 3a和chst 3b，chst 12 a和chst 12 b，dsela和dselb。CS/DS修饰酶的表达在空间和时间上受到调节，不同基因之间存在很大差异。我们发现，CS/DS 4-O-磺基转移酶和6-O-磺基转移酶以及CS/DS差向异构酶显示出强的和部分重叠的表达，而该表达对于具有合成二硫酸化二糖的能力的酶是受限的。结构分析进一步表明，CS/DS硫酸化在胚胎发育过程中增加，主要是由于4-O-硫酸化GalNAc的合成，而6-O-硫酸化GalNAc的比例在后期发育阶段增加。由Chst 15合成的二硫酸化GalNAc和由Ust合成的2-O-硫酸化GlcA/IdoA是罕见的，与这些酶的限制性表达一致。我们还比较了CS/DS组成与硫酸乙酰肝素（HS）。值得注意的是，CS/DS生物合成在早期斑马鱼发育比HS生物合成更动态。此外，HS含有具有多于一个硫酸酯基团的二糖，这在CS/DS中几乎不存在。
Chondroitin/dermatan sulfate (CS/DS) proteoglycans consist of unbranched sulfated polysaccharide chains of repeating GalNAc-GlcA/IdoA disaccharide units, attached to serine residues on specific proteins. The CS/DS proteoglycans are abundant in the extracellular matrix where they have essential functions in tissue development and homeostasis. In this report a phylogenetic analysis of vertebrate genes coding for the enzymes that modify CS/DS is presented. We identify single orthologous genes in the zebrafish genome for the sulfotransferases chst7, chst11, chst13, chst14, chst15 and ust and the epimerase dse. In contrast, two copies were found for mammalian sulfotransferases CHST3 and CHST12 and the epimerase DSEL, named chst3a and chst3b, chst12a and chst12b, dsela and dselb, respectively. Expression of CS/DS modification enzymes is spatially and temporally regulated with a large variation between different genes. We found that CS/DS 4-O-sulfotransferases and 6-O-sulfotransferases as well as CS/DS epimerases show a strong and partly overlapping expression, whereas the expression is restricted for enzymes with ability to synthesize di-sulfated disaccharides. A structural analysis further showed that CS/DS sulfation increases during embryonic development mainly due to synthesis of 4-O-sulfated GalNAc while the proportion of 6-O-sulfated GalNAc increases in later developmental stages. Di-sulfated GalNAc synthesized by Chst15 and 2-O-sulfated GlcA/IdoA synthesized by Ust are rare, in accordance with the restricted expression of these enzymes. We also compared CS/DS composition with that of heparan sulfate (HS). Notably, CS/DS biosynthesis in early zebrafish development is more dynamic than HS biosynthesis. Furthermore, HS contains disaccharides with more than one sulfate group, which are virtually absent in CS/DS.
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影响因子：
3.7
作者：
Hayes AJ;Reynolds S;Nowell MA;Meakin LB;Habicher J;Ledin J;Bashford A;Caterson B;Hammond CL
通讯作者：
Hammond CL
影响因子：
4.8
作者：
Kobayashi, M;Sugumaran, G;Rosenberg, RD
通讯作者：
Rosenberg, RD
影响因子：
4.8
作者：
Maccarana, M;Olander, B;Malmström, A
通讯作者：
Malmström, A
影响因子：
4.3
作者：
Bartolini, Barbara;Thelin, Martin A.;Maccarana, Marco
通讯作者：
Maccarana, Marco
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM