The a-catulin/dystrophin-associated protein complex regulates GPCR function

描述（由申请方提供）：α1-肾上腺素能受体（AR）是G蛋白偶联受体（GPCR），对交感激素去甲肾上腺素和肾上腺素有反应，是治疗高血压、良性前列腺肥大（BPH）和创伤后应激障碍（PTSD）的治疗靶点。α1-AR包括3种独特的亚型，α1A、α1B和α1D，它们在整个CNS的血管上普遍表达。虽然每种亚型都对去甲肾上腺素/肾上腺素有反应并激活Gαq/11信号，但α1D-AR亚型使用与α1A-AR和α1B-AR亚型不同的机制发挥专门作用。例如，α 1D-AR刺激血管平滑肌细胞迁移，而α 1D-AR刺激血管平滑肌细胞迁移。 α1A和α1B-AR亚型刺激血管平滑肌细胞肥大。允许α 1D-AR选择性激活不同于α1A和α1B-AR亚型所使用的途径的分子机制仍然是该领域的一个主要谜团。揭示α 1D-ARs用于刺激血管平滑肌细胞迁移的分子机制将确定新的药物靶点，以治疗CNS血管再狭窄和动脉粥样硬化斑块形成，预防与恶性高血压相关的偏头痛，并降低中风和神经元细胞死亡的可能性。

DESCRIPTION (provided by applicant): α1-adrenergic receptors (ARs) are G-protein coupled receptors (GPCRs) that respond to sympathetic hormones norepinephrine and epinephrine, and are therapeutic targets for the treatment of hypertension, benign prostrate hypertrophy (BPH), and post-traumatic stress disorder (PTSD). α1-ARs comprise 3 unique subtypes, α1A, α1B, and α1D, which are ubiquitously expressed on blood vessels throughout the CNS. Although each subtype responds to norepinephrine/epinephrine and activates Gαq/11 signaling, the α1D-AR subtype performs a specialized role using mechanisms distinct from the α1A-AR and α1B-AR subtypes. For example, α1D-ARs stimulate vascular smooth muscle cell migration, while the α1A and α1B-AR subtypes stimulate vascular smooth cell hypertrophy. The molecular mechanisms that permit α1D-ARs to selectively activate pathways distinct from those used by the α1A and α1B-AR subtypes remains a major mystery in the field. Revealing the molecular mechanisms α1D- ARs use to stimulate vascular smooth cell migration will identify new drug targets to treat CNS blood vessel restenosis and atherosclerotic plaque formation, prevent migraine associated with malignant hypertension and reduce the potential for stroke and neuronal cell death.