Impaired processing of FLP and NLP peptides in carboxypeptidase E (EGL-21)-deficient Caenorhabditis elegans as analyzed by mass spectrometry
Impaired processing of FLP and NLP peptides in carboxypeptidase E (EGL-21)-deficient Caenorhabditis elegans as analyzed by mass spectrometry
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DOI：
10.1111/j.1471-4159.2007.04474.x
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发表时间：
2007-07-01
影响因子：
4.7
通讯作者：
Schoofs, Liliane
中科院分区：
文献类型：
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作者：
Husson, Steven J.;Janssen, Tom;Schoofs, Liliane
生物活性肽是通过加工酶的连续作用从无活性的前蛋白原或肽前体合成的。前蛋白转化酶在成对的碱性氨基酸处裂解前体，然后通过特定的羧肽酶将其从生成的片段的羧基末端去除。缺乏前蛋白转化酶 EGL-3 的秀丽隐杆线虫菌株表现出严重受损的神经肽谱（Husson 等人，2006 年，J. Neurochem.98，1999-2012）。在本研究中，我们研究了线虫羧肽酶 E 直系同源物 EGL-21 在肽前体加工中的作用。在egl-21突变株中检测到超过100个羧基末端延伸的神经肽。这些发现表明 EGL-21 是参与 FMRFamide 样肽 (FLP) 前体和神经肽样蛋白 (NLP) 前体加工的主要羧肽酶。 egl-3 和egl-21 突变体的肽谱受损反映在一些相似的表型中。它们都有严重的肠腔扩张、运动缺陷和胚胎滞留的问题。此外，egl-3动物的肠道脂肪含量降低。总而言之，这些结果表明 EGL-3 和 EGL-21 是神经肽正确加工的关键酶，神经肽控制产蛋、运动、脂肪储存和营养状况。
Biologically active peptides are synthesized from inactive pre-proproteins or peptide precursors by the sequential actions of processing enzymes. Proprotein convertases cleave the precursor at pairs of basic amino acids, which are then removed from the carboxyl terminus of the generated fragments by a specific carboxypeptidase. Caenorhabditis elegans strains lacking proprotein convertase EGL-3 display a severely impaired neuropeptide profile (Husson et al. 2006, J. Neurochem.98, 1999-2012). In the present study, we examined the role of the C. elegans carboxypeptidase E orthologue EGL-21 in the processing of peptide precursors. More than 100 carboxy-terminally extended neuropeptides were detected in egl-21 mutant strains. These findings suggest that EGL-21 is a major carboxypeptidase involved in the processing of FMRFamide-like peptide (FLP) precursors and neuropeptide-like protein (NLP) precursors. The impaired peptide profile of egl-3 and egl-21 mutants is reflected in some similar phenotypes. They both share a severe widening of the intestinal lumen, locomotion defects, and retention of embryos. In addition, egl-3 animals have decreased intestinal fat content. Taken together, these results suggest that EGL-3 and EGL-21 are key enzymes for the proper processing of neuropeptides that control egg-laying, locomotion, fat storage and the nutritional status.