课题基金 / 基金详情

Obesity in Ciliopathies: How Neuronal Primary Cilia Control Appetite

Obesity in Ciliopathies: How Neuronal Primary Cilia Control Appetite
纤毛病中的肥胖:神经元初级纤毛如何控制食欲
批准号:
9234008
负责人:
Jeremy F Reiter
金额:
$67.86万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-06-01 至 2020-04-30

项目摘要

项目成果

Jeremy F Reiter的其他基金

相似基金

相关文献

中文摘要
翻译

英文摘要
 DESCRIPTION (provided by applicant): Our studies address how neuronal primary cilia control obesity. The primary cilium is a cell surface projection that receives and transduces select extracellular signals. In humans, mutations that disrupt the function of primary cilia cause ciliopathies, pleiotropic diseases of which obesity is a cardinal manifestation. How ciliary dysfunction leads to obesity is unclear, but is thought to involve disruption of neuronal signaling pathways that regulate energy homeostasis. The Melanocortin-4 receptor (MC4R) is a central mediator of the regulation of long-term energy homeostasis and mutations in MC4R are the most common monogenic cause of severe human obesity. We have found that MC4R and the recently described MC4R associated protein MRAP2 localize to the primary cilia and that disruption of primary cilia abolishes the anorexigenic function of MC4R in mice. These results suggest three important hypotheses: 1) MC4R functions at the cilium. 2) The endogenous MC4R ligands, αMSH and AGRP, are sensed by the second order MC4R-expressing neurons through their primary cilia, making this non- synaptic mechanism of modulating neuronal activity an important component of long-term energy homeostasis. 3) Disruption of MC4R signaling is the cause of obesity in ciliopathies. We will test these hypotheses by identifying how MC4R and MRAP2 are targeted to cilia, how ciliopathy-associated proteins participate in MC4R function, and how these proteins signal through cilia to indicate satiety. This work will define molecular and cellular steps of neuronal regulation of energy homeostasis and answer the long-standing question of how ciliary dysfunction causes obesity in humans.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Illuminating the function of the understudied kinase DYRK2 in ciliary Hedgehog signal transduction
Obesity in ciliopathies: How neuronal primary cilia control appetite
Understanding Ciliary Functions in Mammalian Development
Understanding Ciliary Functions in Mammalian Development
海外基金