Gerdes J M, Katsanis N
McKusick-Nathans Institute of Genetic Medicine, John Hopkins University, 533 Broadway Research Building, 733 N. Broadway, Baltimore, Maryland 21205, USA.
Cell Mol Life Sci. 2005 Jul;62(14):1556-70. doi: 10.1007/s00018-005-5007-5.
Microtubules are primarily responsible for facilitating long-distance transport of both proteins and organelles. Given the critical role of this process in cellular function, it is not surprising that perturbation of microtubule-based transport can lead to diverse phenotypes in humans, including cancer and neurodegenerative disorders such as Alzheimer or Huntington disease. Recent investigations have also indicated that defects in specialized microtubule-based transport systems, such as mutations affecting the transport of protein particles along the length of cilia (intraflagellar transport) can cause retinal dystrophy, polycystic kidney disease or more complex syndromic phenotypes, such as Bardet-Biedl syndrome. In this review, we discuss recent findings implicating defects in microtubule-associated transport and motor proteins in a variety of diseases, particularly the role of defective microtubular transport in neurological and ciliary disease. These defects frequently display phenotypic consequences that manifest as human disease yet do not cause organismal lethality.
微管主要负责促进蛋白质和细胞器的长距离运输。鉴于这一过程在细胞功能中发挥的关键作用，基于微管的运输受到干扰会导致人类出现多种表型，包括癌症以及阿尔茨海默病或亨廷顿病等神经退行性疾病，也就不足为奇了。最近的研究还表明，基于微管的特殊运输系统存在缺陷，例如影响蛋白质颗粒沿纤毛长度运输的突变（鞭毛内运输），可导致视网膜营养不良、多囊肾病或更复杂的综合征表型，如巴德-比埃尔综合征。在这篇综述中，我们讨论了最近的研究发现，这些发现表明微管相关运输和驱动蛋白的缺陷与多种疾病有关，特别是微管运输缺陷在神经疾病和纤毛疾病中的作用。这些缺陷常常表现出作为人类疾病的表型后果，但不会导致生物体死亡。
