Bounoutas Alexander, O'Hagan Robert, Chalfie Martin
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Curr Biol. 2009 Aug 25;19(16):1362-7. doi: 10.1016/j.cub.2009.06.036. Epub 2009 Jul 16.
Because microtubules perform many essential functions in neurons, delineating unique roles attributable to these organelles presents a formidable challenge. Microtubules endow neurons with shape and structure and are required for developmental processes including neurite outgrowth, intracellular transport, and synapse formation and plasticity; microtubules in sensory neurons may be required for the above processes in addition to a specific sensory function. In Caenorhabditis elegans, six touch receptor neurons (TRNs) sense gentle touch and uniquely contain 15-protofilament microtubules. Disruption of these microtubules by loss of either the MEC-7 beta-tubulin or MEC-12 alpha-tubulin or by growth in 1 mM colchicine causes touch insensitivity, altered distribution of the touch transduction channel, and a general reduction in protein levels. We show that the effect on touch sensitivity can be separated from the others; microtubule depolymerization in mature TRNs causes touch insensitivity but does not result in protein distribution and production defects. In addition, the mec-12(e1605) mutation selectively causes touch insensitivity without affecting microtubule formation and other cellular processes. Touching e1605 animals produces a reduced mechanoreceptor current that inactivates more rapidly than in wild-type, suggesting a specific role of the microtubules in mechanotransduction.
由于微管在神经元中执行许多重要功能,因此描述这些细胞器的独特作用是一项艰巨的挑战。微管赋予神经元形状和结构,是包括神经突生长、细胞内运输、突触形成和可塑性等发育过程所必需的;感觉神经元中的微管除了具有特定的感觉功能外,可能也是上述过程所必需的。在秀丽隐杆线虫中,六个触觉受体神经元(TRN)感知轻柔触摸,并且独特地含有15根原纤维微管。通过缺失MEC-7β-微管蛋白或MEC-12α-微管蛋白,或通过在1 mM秋水仙碱中生长来破坏这些微管,会导致触觉不敏感、触觉转导通道分布改变以及蛋白质水平普遍降低。我们表明,对触觉敏感性的影响可以与其他影响分开;成熟TRN中的微管解聚会导致触觉不敏感,但不会导致蛋白质分布和产生缺陷。此外,mec-12(e1605)突变选择性地导致触觉不敏感,而不影响微管形成和其他细胞过程。触摸e1605动物会产生比野生型更快失活的降低的机械感受器电流,这表明微管在机械转导中具有特定作用。