The Caenorhabditis elegans vab-10 spectraplakin isoforms protect the epidermis against internal and external forces.
The Caenorhabditis elegans vab-10 spectraplakin isoforms protect the epidermis against internal and external forces.
复制标题
DOI：
10.1083/jcb.200302151
复制
发表时间：
2003-05-26
影响因子：
7.8
通讯作者：
Labouesse, Michel
中科院分区：
文献类型：
--
作者：
Bosher, Julia M;Hahn, Bum-Soo;Legouis, Renaud;Sookhareea, Satis;Weimer, Robby M;Gansmuller, Anne;Chisholm, Andrew D;Rose, Ann M;Bessereau, Jean-Louis;Labouesse, Michel
秀丽线虫胚胎的形态发生是由表皮中的肌动蛋白微丝和体壁肌肉中的肌节驱动的。这两种组织是机械连接的，很可能是通过称为纤维细胞器(FOS)的专门连接结构来连接肌肉和跨越表皮的角质层。在这里，我们报告了一种被称为VAB-10的基因的新突变的鉴定，该突变会导致严重的形态发生缺陷，并表明VAB-10对应于线虫spectraplakin基因座。我们对VAB-10的分析揭示了对这个Plakin亚家族的作用的新见解。VAB-10产生与凝集素(称为VAB-10A)或微管肌动蛋白交联因子Plakins(称为VAB-10B)相关的异构体。利用特定的抗体和突变，我们证明了VAB-10A和VAB-10B在表皮中具有不同的分布和功能。VAB-10A的缺失破坏了FOS的完整性，导致表皮脱离角质层和肌肉，从而证明FOS在功能和分子上与半桥粒有关。我们认为这种异构体可以保护皮肤免受外力的侵袭。相反，在胚胎形态发生过程中，当表皮细胞改变形状时，缺乏VAB-10B会导致表皮厚度增加。我们认为，这种异构体保护细胞免受表皮内形成的张力的影响。
Morphogenesis of the Caenorhabditis elegans embryo is driven by actin microfilaments in the epidermis and by sarcomeres in body wall muscles. Both tissues are mechanically coupled, most likely through specialized attachment structures called fibrous organelles (FOs) that connect muscles to the cuticle across the epidermis. Here, we report the identification of new mutations in a gene known as vab-10, which lead to severe morphogenesis defects, and show that vab-10 corresponds to the C. elegans spectraplakin locus. Our analysis of vab-10 reveals novel insights into the role of this plakin subfamily. vab-10 generates isoforms related either to plectin (termed VAB-10A) or to microtubule actin cross-linking factor plakins (termed VAB-10B). Using specific antibodies and mutations, we show that VAB-10A and VAB-10B have distinct distributions and functions in the epidermis. Loss of VAB-10A impairs the integrity of FOs, leading to epidermal detachment from the cuticle and muscles, hence demonstrating that FOs are functionally and molecularly related to hemidesmosomes. We suggest that this isoform protects against forces external to the epidermis. In contrast, lack of VAB-10B leads to increased epidermal thickness during embryonic morphogenesis when epidermal cells change shape. We suggest that this isoform protects cells against tension that builds up within the epidermis.