C-elegans pharyngeal morphogenesis requires both de novo synthesis of pyrimidines and synthesis of heparan sulfate proteoglycans
C-elegans pharyngeal morphogenesis requires both de novo synthesis of pyrimidines and synthesis of heparan sulfate proteoglycans
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DOI：
10.1016/j.ydbio.2006.06.008
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发表时间：
2006-08-15
影响因子：
2.7
通讯作者：
Okkema, Peter G.
中科院分区：
文献类型：
--
作者：
Franks, Dawn M.;Izumikawa, Tomomi;Okkema, Peter G.
梭在胚胎发生的2倍和3倍阶段之间，秀丽线虫咽经历伸长和形态发生，形成其特征性的双叶形状。在此期间，咽肌和边缘细胞形成前、后咽球之间的峡部，并伸长和变窄。我们已经确定了自发突变体pyr-1（cu 8）表现出缺陷的咽峡部延长，细胞骨架组织缺陷，和母体效应致死。pyr-1编码CAD，一种从头嘧啶合成所需的三功能酶，并且通过提供外源嘧啶来拯救pyr-1（cu 8）突变体。在sqv-1、sqv-8、rib-1和rib-2突变体中发现了类似的咽部缺陷和母体效应致死性，这些突变体影响参与硫酸乙酰肝素蛋白聚糖（HSPG）合成的酶。rib-1突变体致死率在pyr-1突变体背景下增强，表明HSPG合成对减少的嘧啶库非常敏感，并且HS二糖在rib-1和pyr-1突变体中均适度减少。我们推测，HSPG是必要的咽峡部的伸长，和pyr-1的功能上游的蛋白聚糖合成酶，通过提供的UDP-糖HSPG合成所必需的前体。(c)2006年爱思唯尔公司All rights reserved.
The C. elegans pharynx undergoes elongation and morphogenesis to its characteristic bi-lobed shape between the 2- and 3-fold stages of embryogenesis. During this period, the pharyngeal muscles and marginal cells forming the isthmus between the anterior and posterior pharyngeal bulbs elongate and narrow. We have identified the spontaneous mutant pyr-1(cu8) exhibiting defective pharyngeal isthmus elongation, cytoskeletal organization defects, and maternal effect lethality. pyr-1 encodes CAD, a trifunctional enzyme required for de novo pyrimidine synthesis, and pyr-1(cu8) mutants are rescued by supplying exogenous pyrimidines. Similar pharyngeal defects and maternal effect lethality were found in sqv-1, sqv-8, rib-1 and rib-2 mutants, which affect enzymes involved in heparan sulfate proteoglycan (HSPG) synthesis. rib-1 mutant lethality was enhanced in a pyr-1 mutant background, indicating that HSPG synthesis is very sensitive to decreased pyrimidine pools, and HS disaccharides are moderately decreased in both rib-1 and pyr-1 mutants. We hypothesize that HSPGs are necessary for pharyngeal isthmus elongation, and pyr-1 functions upstream of proteoglycan synthesizing enzymes by providing precursors of UDP-sugars essential for HSPG synthesis. (c) 2006 Elsevier Inc. All rights reserved.