骨骼发育不良是一组罕见的遗传疾病,由编码软骨细胞外基质(ECM)结构蛋白的基因突变引起,信号分子,转录因子,表观遗传修饰剂,和几种细胞内蛋白质。细胞分裂,细胞器维护,细胞内运输都是由细胞骨架相关的蛋白质协调的,通过微管相关运动影响的细胞内过程对骨骼细胞的功能很重要。在微管相关运动蛋白中,特别是驱动蛋白已被证明在细胞周期动力学中起关键作用,包括染色体分离,有丝分裂纺锤体形成和纤毛发生,除了货物贩运,受体再循环和内吞作用。最近的研究强调了驱动蛋白在胚胎发育和形态发生中的基本作用,并表明驱动蛋白基因的突变会导致几种骨骼发育不良。然而,关于驱动蛋白及其衔接分子的特定功能以及在骨骼发育过程中驱动蛋白参与的特定分子机制的许多问题仍未得到解答。在这里,我们对驱动蛋白缺陷导致的骨骼发育不良进行了综述,并讨论了驱动蛋白在骨骼发育过程中活跃的分子机制中的参与。
Skeletal dysplasias are group of rare genetic diseases resulting from mutations in genes encoding structural proteins of the cartilage extracellular matrix (ECM), signaling molecules, transcription factors, epigenetic modifiers, and several intracellular proteins. Cell division, organelle maintenance, and intracellular transport are all orchestrated by the cytoskeleton-associated proteins, and intracellular processes affected through microtubule-associated movement are important for the function of skeletal cells. Among microtubule-associated motor proteins, kinesins in particular have been shown to play a key role in cell cycle dynamics, including chromosome segregation, mitotic spindle formation, and ciliogenesis, in addition to cargo trafficking, receptor recycling, and endocytosis. Recent studies highlight the fundamental role of kinesins in embryonic development and morphogenesis and have shown that mutations in
kinesin genes lead to several skeletal dysplasias. However, many questions concerning the specific functions of kinesins and their adaptor molecules as well as specific molecular mechanisms in which the
kinesin proteins are involved during skeletal development remain unanswered. Here we present a
review of the skeletal dysplasias resulting from defects in kinesins and discuss the involvement of
kinesin proteins in the molecular mechanisms that are active during skeletal development.