Galou M, Gao J, Humbert J, Mericskay M, Li Z, Paulin D, Vicart P
Laboratoire de Biologie Moléculaire de la Différentiation de l'Université Paris 7, France.
Biol Cell. 1997 May;89(2):85-97.
Research over the past few years on the function of intermediate filaments in cells in culture has not produced convincing results, because the key role of intermediate filaments is within tissues and at certain periods of development. Only recently the technique of gene knockout has been used to examine intermediate filaments in mice and has provided the first evidence that intermediate filaments are directly involved in cell resilience and the maintenance of tissue integrity. Knockout of the gene encoding keratin K8 is lethal in the embryo, and results in hepatic or intestinal lesions, while knockout of the K14 or K10 genes leads to rupture of stratified epithelia. Knockout of the gene encoding desmin causes the rupture of skeletal and cardiac muscle, and collapse of blood vessel walls. Knockout of the gene coding for GFAP leads to a loss of cerebral white matter, and knockout of the gene coding for vimentin causes degeneration of the cerebellar Purkinje cells. The results reveal the lack of compensation by another intermediate filament. Tissues without intermediate filaments fall apart; they are mechanically unstable, unable to resist physical stress, and this leads to cell degeneration. By maintaining the shape and plasticity of the cell, the intermediate filament network acts as an integrator within the cell space. The state of mechanical force imposed on a tissue or a cell can alter the shape of certain elements of the cytoskeleton and thus participate to the control of cell functions.
过去几年对培养细胞中中间丝功能的研究并未得出令人信服的结果，因为中间丝的关键作用体现在组织中以及特定的发育阶段。直到最近，基因敲除技术才被用于研究小鼠体内的中间丝，并首次提供证据表明中间丝直接参与细胞弹性和组织完整性的维持。编码角蛋白K8的基因敲除在胚胎期是致死的，并会导致肝脏或肠道损伤，而K14或K10基因的敲除会导致复层上皮破裂。编码结蛋白的基因敲除会导致骨骼肌和心肌破裂以及血管壁塌陷。编码胶质纤维酸性蛋白（GFAP）的基因敲除会导致脑白质丧失，而编码波形蛋白的基因敲除会导致小脑浦肯野细胞退化。这些结果表明不存在其他中间丝的代偿作用。没有中间丝的组织会解体；它们在机械上不稳定，无法抵抗物理压力，进而导致细胞退化。通过维持细胞的形状和可塑性，中间丝网络在细胞空间内起到整合作用。施加在组织或细胞上的机械力状态可以改变细胞骨架某些成分的形状，从而参与对细胞功能的控制。
