Lowe syndrome: Between primary cilia assembly and Rac1-mediated membrane remodeling.
Lowe syndrome: Between primary cilia assembly and Rac1-mediated membrane remodeling.
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Lowe综合征：原发性纤毛组装和Rac1介导的膜重塑。
DOI：
10.4161/cib.21952
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发表时间：
2012-11-01
影响因子：
--
通讯作者：
Aguilar RC
中科院分区：
文献类型：
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作者：
Madhivanan K;Mukherjee D;Aguilar RC
洛氏综合征（LS）是一种致命的x连锁遗传病，由磷脂肌醇5-磷酸酶（ocl1）的功能缺陷引起。在过去的四年中，我们的实验室使用来自LS患者的真皮成纤维细胞描述了第一个ocrl1特异性细胞表型。这些表型在ocl1 -morphant斑马鱼模型中得到验证，包括膜重塑（细胞迁移/扩散、液相摄取）缺陷和初级纤毛组装异常。一方面，我们的发现揭示了细胞表型可能与观察到的发育缺陷有关；另一方面，这些发现确立了LS是一种与纤毛病相关的疾病。本文讨论了Ocrl1功能丧失可能影响RhoGTPase信号通路的机制，从而导致肌动蛋白细胞骨架重排，从而导致观察到的细胞表型。
Lowe syndrome (LS) is a lethal X-linked genetic disease caused by functional deficiencies of the phosphatidlyinositol 5-phosphatase, Ocrl1. In the past four years, our lab described the first Ocrl1-specific cellular phenotypes using dermal fibroblasts from LS patients. These phenotypes, validated in an ocrl1-morphant zebrafish model, included membrane remodeling (cell migration/spreading, fluid-phase uptake) defects and primary cilia assembly abnormalities. On one hand, our findings unraveled cellular phenotypes likely to be involved in the observed developmental defects; on the other hand, these discoveries established LS as a ciliopathy-associated disease. This article discusses the possible mechanisms by which loss of Ocrl1 function may affect RhoGTPase signaling pathways leading to actin cytoskeleton rearrangements that underlie the observed cellular phenotypes.