Norman K R, Moerman D G
Department of Zoology, University of British Columbia, Vancouver, British Columbia, V6T 1Z4, Canada.
Dev Biol. 2000 Nov 15;227(2):690-705. doi: 10.1006/dbio.2000.9897.
Basement membranes are thin sheets of specialized extracellular matrix molecules that are important for supplying mechanical support and for providing an interactive surface for cell morphology. Prior to secretion and assembly, basement membrane molecules undergo intracellular processing, which is essential for their function. We have identified several mutations in a procollagen processing enzyme, lysyl hydroxylase (let-268). The Caenorhabditis elegans lysyl hydroxylase is highly similar to the vertebrate lysyl hydroxylase, containing all essential motifs required for enzymatic activity, and is the only lysyl hydroxylase found in the C. elegans sequenced genome. In the absence of C. elegans lysyl hydroxylase, type IV collagen is expressed; however, it is retained within the type IV collagen-producing cells. This observation indicates that in let-268 mutants the processing and secretion of type IV collagen is disrupted. Our examination of the body wall muscle in these mutant animals reveals normal myofilament assembly prior to contraction. However, once body wall muscle contraction commences the muscle cells separate from the underlying epidermal layer (the hypodermis) and the myofilaments become disorganized. These observations indicate that type IV collagen is required in the basement membrane for mechanical support and not for organogenesis of the body wall muscle.
基底膜是由特殊细胞外基质分子构成的薄片，对于提供机械支持以及为细胞形态提供相互作用表面至关重要。在分泌和组装之前，基底膜分子会经历细胞内加工，这对其功能至关重要。我们在一种原胶原蛋白加工酶——赖氨酰羟化酶（let-268）中鉴定出了几种突变。秀丽隐杆线虫的赖氨酰羟化酶与脊椎动物的赖氨酰羟化酶高度相似，包含酶活性所需的所有必需基序，并且是在秀丽隐杆线虫测序基因组中发现的唯一一种赖氨酰羟化酶。在缺乏秀丽隐杆线虫赖氨酰羟化酶的情况下，IV型胶原蛋白会表达；然而，它会保留在产生IV型胶原蛋白的细胞内。这一观察结果表明，在let-268突变体中，IV型胶原蛋白的加工和分泌受到了破坏。我们对这些突变动物的体壁肌肉进行检查发现，在收缩之前肌丝组装正常。然而，一旦体壁肌肉开始收缩，肌肉细胞就会与下方的表皮层（皮下组织）分离，肌丝也会变得紊乱。这些观察结果表明，基底膜中的IV型胶原蛋白对于机械支持是必需的，而对于体壁肌肉的器官发生则不是必需的。
