Cilia-specific cAMP plays a major role in aneurysm

项目说明 环磷酸腺苷(CAMP)信号调节多种途径和细胞功能 在被区分时的具体反应。然而，cAMP在纤毛功能中的作用还知之甚少。 尽管cAMP在纤毛疾病的发展中有一定的意义。使用两种新技术，纳米颗粒 药物传递和单细胞成像系统，我们的初步数据表明cAMP在 纤毛可能独立于胞质中的纤毛。此外，我们有初步证据表明，抑制 磷酸二酯酶-3(PDE3)是cAMP的失活剂，可以恢复睫状体病变模型的睫状体功能。 容易发生动脉瘤，而动脉瘤血管的特征是基因组不稳定。在这里，我们假设 纤毛cAMP在动脉瘤的形成中起着重要作用，我们建议测试PDE3是否参与了 通过基因组不稳定导致的血管动脉瘤(AIM 1)，并阐明其在初级纤毛中cAMP信号转导中的作用(AIM 2)。总体而言，我们将测试单个纤毛是否可以作为响应PDE/cAMP的关键传感器 车厢。

PROJECT DESCRIPTION Cyclic adenosine monophosphate (cAMP) signaling regulates diverse pathways and cellular functions that result in specific responses when compartmentalized. However, the role of cAMP in cilia function is poorly understood, despite the implication of cAMP in the development of ciliopathies. Using two novel techniques, nanoparticle drug delivery and a single-cell imaging system, our preliminary data indicate that changes in cAMP within a cilium could be independent from those in the cytosol. Furthermore, we have preliminary evidence that inhibition of phosphodiesterase-3 (PDE3), an inactivator of cAMP, can restore ciliary function in ciliopathy models that are prone to aneurysm, and that aneurysmal vessels are characterized by genomic instability. Here, we hypothesize that ciliary cAMP plays an important role in aneurysm formation, and we propose to test if PDE3 is involved in vascular aneurysm via genomic instability (Aim 1) and clarify its role in cAMP signaling in primary cilia (Aim 2). Overall, we will test the idea if a single cilium could be a critical sensor acting as a responsive PDE/cAMP compartment.