Titin/connectin-related proteins in C-elegans:: a review and new findings
Titin/connectin-related proteins in C-elegans:: a review and new findings
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DOI：
10.1007/s10974-005-9027-4
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发表时间：
2005-12-01
影响因子：
2.7
通讯作者：
Benian, Guy M.
中科院分区：
文献类型：
--
作者：
Ferrara, Tracey M.;Flaherty, Denise B.;Benian, Guy M.
关于肌原纤维从其组成部分组装的机制，以及这些精确的结构如何在重复的肌肉活动中保持，仍然有很多未知之处。许多实验室，包括我们的实验室，都在利用这种能力来分析线虫C。来获得对这些问题的见解。C.线虫是研究肌肉的特别有吸引力的生物体（Waterston，1988; Moerman和Fire，1997）。先进的正向和最近的反向遗传方法可用于揭示表型。通常的自花受精使肌肉突变体繁殖，使动物如此不协调，他们将无法交配。光学透明度允许通过偏振光显微镜评估肌肉结构。用于运动的肌肉位于体壁中（图1）。在成人中，有95个梭形单核细胞，分为四个象限，位于基底膜、皮下组织和角质层下面。在每个象限中，细胞以互锁的方式排列。偏振光显微镜下可见明显的条纹;明亮的（双折射）A带与黑暗的I带交替出现;每个I带包含一排致密体，它们类似于脊椎动物横纹肌中的Z盘。由于横纹相对于动物的长轴呈略微倾斜的角度，因此这种肌肉被称为“斜横纹”。相反，脊椎动物横纹肌，其中肌原纤维填充整个细胞，在线虫体壁肌肉，相当于肌丝晶格被限制在一个狭窄的区域1.5 lm的外侧的细胞，细胞膜下面。细纤维附着在致密体上，粗纤维围绕M线排列。所有致密体和M线都锚定在肌细胞膜上，肌细胞膜附着在皮下组织和角质层上。这使得肌肉收缩的力量直接传递到角质层，并允许整个动物的运动。因此，蠕虫肌肉M线和致密体的功能与脊椎动物肌肉中的类似结构相似。但是，此外，由于它们的膜锚定和蛋白质组成，它们也类似于脊椎动物的非肌肉局灶性粘连。第二大肌肉群位于咽部，咽部是蠕虫前部附近的神经肌肉泵，用于在进入肠道之前泵入和研磨细菌。线虫肌原纤维及其膜-细胞外基质附着结构。这些蛋白质中的大多数首先通过突变来定义，大多数属于两个表型类别之一。在一个类别中，不协调或“Unc”类，动物在成年后移动缓慢或瘫痪。第二类，“Pat”类突变体（在二倍时瘫痪停滞）具有特征性的胚胎致死性，其中胚胎不在蛋壳内移动并且在二倍阶段停止发育（威廉姆斯和Waterston，1994）。一些基因具有功能丧失的Unc和无效Pat表型;实例包括unc-97（PINCH）（Hobert et al. 1999）和unc-45（肌球蛋白伴侣，UCS家族成员）（Barral等，1998年）。到目前为止，已经有五组蛋白质被证明是C.秀丽线虫：（1）twitchin，（2）tetchin-89，（3）Ce titin，（4）DIM-1（Rogalski等，2003），和（5）Kettin。这篇综述将集中在我们目前的理解twitchin，ESTA-89和Ce肌联蛋白，因为这些已经，或目前正在研究，在我们的实验室。Kettin已经在果蝇中得到了很好的研究...
Much is still unknown about mechanisms by which myofibrils assemble from their components, and how these precise structures are maintained in the face of repeated muscle activity. A number of labs, including ours, are exploiting the ability to analyze mutants in the nematode C. elegans to obtain insights into these questions. C. elegans is a particularly attractive organism in which to study muscle (Waterston, 1988; Moerman and Fire, 1997). Sophisticated forward, and more recently, reverse genetic approaches are available to reveal phenotypes. The usual self-fertilization allows propagation of muscle mutants that render animals so uncoordinated that they would be unable to mate. Optical transparency allows evaluation of muscle structure by polarized light microscopy. The muscles used for locomotion reside in the body wall (Figure 1). In the adult, there are 95 spindle shaped mononuclear cells divided amongst four quadrants just underlying a basement membrane, hypodermis and cuticle. In each quadrant, the cells are arranged in interlocking pairs. By polarized light microscopy, obvious striations are seen; bright (birefringent) A-bands alternate with dark I-bands; each I-band contains a row of dense bodies, which are the analogs of Z-discs in vertebrate striated muscle. Because the striations lie at a slightly oblique angle with respect to the long axis of the animal, this muscle is called ‘obliquely striated’. In contrast to vertebrate striated muscle, in which myofibrils fill the entire cell, in nematode body wall muscle, the equivalent myofilament lattice is restricted to a narrow zone of $1.5 lm on the outer side of the cell, just beneath the cell membrane. The thin filaments are attached to the dense bodies, and the thick filaments are organized around M-lines. All the dense bodies and M-lines are anchored to the muscle cell membrane, which is attached to the hypodermis and cuticle. This allows the force of muscle contraction to be transmitted directly to the cuticle and allows movement of the whole animal. Thus, worm muscle M-lines and dense bodies serve the function of analogous structures in vertebrate muscle. But, in addition, because of their membrane anchorage and protein composition, they are also similar to vertebrate non-muscle focal adhesions. The second largest set of muscle resides in the pharynx, the neuromuscular pump near the front of the worm used for pumping-in and grinding-up bacteria before passage into the intestine.Studies during the past 30 years in over a dozen labs have defined many components of C. elegans myofibrils and their membrane-extracellular matrix attachment structures. Most of these proteins were first defined through mutations–most falling into one of two phenotypic classes. In one class, the uncoordinated or ‘Unc’class, animals are slow moving or paralyzed as adults. The second class, the ‘Pat’class of mutants (paralyzed arrested at two-fold) have a characteristic embryonic lethality in which embryos do not move within the eggshell and stop development at the twofold stage (Williams and Waterston, 1994). A few genes have loss-of-function Unc and null Pat phenotypes; examples include unc-97 (PINCH)(Hobert et al., 1999) and unc-45 (myosin chaperone, UCS family member)(Barral et al., 1998). To date, five sets of proteins have been shown to be members of the intracellular, mostly muscle branch of the Ig superfamily in C. elegans:(1) twitchin,(2) UNC-89,(3) Ce titin,(4) DIM-1 (Rogalski et al., 2003), and (5) kettin. This review will focus on our current understanding of twitchin, UNC-89 and Ce titin, as these have been, or are currently, being studied in our laboratory. Kettin has been well studied in Drosophila …