The retinitis pigmentosa 1 protein is a photoreceptor microtubule- associated protein
The retinitis pigmentosa 1 protein is a photoreceptor microtubule- associated protein
复制标题
DOI：
10.1523/jneurosci.1335-04.2004
复制
发表时间：
2004-07-21
影响因子：
5.3
通讯作者：
Pierce, EA
中科院分区：
文献类型：
--
作者：
Liu, Q;Zuo, J;Pierce, EA
视杆细胞和视锥细胞的外节是高度特化的感觉纤毛，其由数百个膜盘沿感光体轴丝沿着有序排列而成。目前还不清楚外节盘的排列是如何控制的，尽管有人认为轴丝可能在这一过程中发挥作用。视网膜色素变性1（RP 1）基因突变是视网膜色素变性（RP）的常见原因。在小鼠中Rp 1基因的破坏导致外节盘的定向错误，这表明RP 1在外节组织中的作用。在这里，我们表明，RP 1蛋白是感光体轴丝的一部分。RP 1的氨基酸28-228与神经元微管相关蛋白（MAP）双皮质素的微管结合结构域具有有限的同源性，介导RP 1和微管之间的相互作用，表明RP 1中推定的双皮质素（DCX）结构域是功能性的。RP 1的N-末端部分在体外刺激微管的形成并稳定异源细胞中的细胞质微管。对来自Rp 1基因靶向破坏的小鼠的光感受器轴丝的评估表明，含有DCX结构域的Rp 1蛋白也有助于控制体内轴丝的长度和稳定性。这些结果表明RP 1是MAP。鉴于RP 1在光感受器中的特异性表达，RP 1因此是待鉴定的第一个光感受器特异性MAP。此外，这些发现表明，RP 1形式的遗传性视网膜变性是由MAP功能障碍引起的更大类别的神经退行性疾病的一部分。
The outer segments of rod and cone photoreceptor cells are highly specialized sensory cilia made up of hundreds of membrane discs stacked into an orderly array along the photoreceptor axoneme. It is not known how the alignment of the outer segment discs is controlled, although it has been suggested that the axoneme may play a role in this process. Mutations in the retinitis pigmentosa 1 (RP1) gene are a common cause of retinitis pigmentosa ( RP). Disruption of the Rp1 gene in mice causes misorientation of outer segment discs, suggesting a role for RP1 in outer segment organization. Here, we show that the RP1 protein is part of the photoreceptor axoneme. Amino acids 28-228 of RP1, which share limited homology with the microtubule- binding domains of the neuronal microtubule-associated protein ( MAP) doublecortin, mediate the interaction between RP1 and microtubules, indicating that the putative doublecortin (DCX) domains in RP1 are functional. The N-terminal portion of RP1 stimulates the formation of microtubules in vitro and stabilizes cytoplasmic microtubules in heterologous cells. Evaluation of photoreceptor axonemes from mice with targeted disruptions of the Rp1 gene shows that Rp1 proteins that contain the DCX domains also help control axoneme length and stability in vivo. These results demonstrate that RP1 is a MAP. Given the specific expression of RP1 in photoreceptors, RP1 is thus the first photoreceptor-specific MAP to be identified. Furthermore, these findings indicate that the RP1 form of inherited retinal degeneration is part of the larger class of neuro-degenerative diseases caused by MAP dysfunction.