Role of mechanically activated ion channels in somatosensation

机械激活离子通道在体感中的作用

• 批准号: 9982299
• 负责人: Ardem Patapoutian
• 金额: $ 48.13万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-12 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982299
• 关键词: Ablation; Address; Adult; Affect; Afferent Neurons; Anatomy; Apnea; Area; Biological Assay; Biology; Birth; Bladder; Breathing; Cations; Cells; Cephalic; Chest; Cleft Palate; Clinic; Complement; Complex; Data; Disease; Engineering; Fiber; Ganglia; Gases; Genetic; Gordon syndrome; Head; Human; Impairment; In Vitro; Ion Channel; Knockout Mice; Lead; Lung; Lung diseases; Mechanical Stimulation; Mechanics; Molecular; Mus; Muscle; Mutation; Neural Crest; Neuroepithelial Bodies; Neurons; Newborn Infant; Nodose Ganglion; Organ; Pain; Pathway interactions; Patients; Phenotype; Physiological; Piezo 1 ion channel; Piezo 2 ion channel; Play; Plethysmography; Population; Proprioception; Reflex action; Respiration; Respiratory Signs and Symptoms; Respiratory System; Respiratory distress; Respiratory physiology; Rest; Role; Sensory; Sensory Ganglia; Shapes; Signal Transduction; Skin; Spinal Ganglia; Stimulus; Stomach; Stretching; Testing; Tidal Volume; Tissues; Tooth structure; Touch sensation; Trigeminal System; Whole Body Plethysmography; bone; conditional knockout; craniofacial; craniofacial tissue; experience; experimental study; gain of function; gain of function mutation; insight; knock-down; loss of function; mechanical force; mechanotransduction; nerve supply; neuronal cell body; optogenetics; promoter; respiratory; response; sensor; somatosensory

PROJECT SUMMARY/ABSTRACT Somatosensory neurons that innervate the skin and muscle play an essential role in sensing touch, pain, and proprioception. The same type of sensory neurons innervates other organs that experience frequent mechanical stimulation. This list of such organs/tissues includes bone, teeth, lung, vasculature, stomach, and bladder. Anatomically, cranial ganglia (including trigeminal) innervate the head, while nodose/jugular and dorsal root ganglia (DRG) innervate the rest of the body. The role of the mechanically activated (MA) non-selective cation channel Piezo2 in DRGs for sensing touch and proprioception is well established. However, much less is known about the role of Piezo2 (and mechanotransduction in general) in other sensory ganglia that innervate the craniofacial region and other internal organs. For example, repetitive and wide-ranging mechanical forces are experienced by our respiratory system. Lung stretch is sensed by neurons with their cell bodies in the nodose/jugular, trigeminal, and thoracic DRGs. Mechanically-driven reflexes are thought to be crucial for proper lung function; however, the precise physiological significance and molecular mechanism of mechanotransduction within the lung remains obscure. In preliminary data presented in this proposal, we show that Piezo2 is expressed in neurons innervating the airways. We further show that global and sensory neuronspecific ablation of Piezo2 causes symptoms of respiratory distress. Building on the preliminary data presented here, we will investigate the role of Piezo2 in respiration and in various craniofacial tissues.

项目总结/摘要 支配皮肤和肌肉的躯体感觉神经元在感觉中起重要作用 触觉、疼痛和本体感受。同样类型的感觉神经元支配其他器官， 频繁的机械刺激。这些器官/组织的列表包括骨， 牙齿、肺、脉管系统、胃和膀胱。在解剖学上，颅神经节（包括 三叉神经节支配头部，而结状/颈静脉和背根神经节（DRG）支配头部 身体的其余部分。机械激活（MA）非选择性阳离子通道的作用 用于感测触摸和本体感觉的DRG中的Piezo 2已被充分确立。然而，远不如 已知Piezo 2（和一般的机械转导）在其他感觉神经节中的作用 支配颅面区域和其他内部器官的神经。例如，重复和 我们的呼吸系统经受广泛的机械力。肺伸展是 由结节/颈静脉、三叉神经和胸DRG中的神经元用其细胞体感知。 机械驱动的反射被认为对适当的肺功能至关重要;然而， 机械力传导的确切生理意义和分子机制 肺部仍然模糊不清。在本提案中提出的初步数据中，我们表明Piezo 2是 在支配呼吸道的神经元中表达。我们进一步表明，全球和感觉神经元特异性 Piezo 2的消融导致呼吸窘迫症状。在初步 本文提供的数据，我们将研究Piezo 2在呼吸中的作用， 颅面组织

项目成果

Piezo2 is the major transducer of mechanical forces for touch sensation in mice.

• DOI: 10.1038/nature13980
• 发表时间: 2014-12-04
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Ranade, Sanjeev S.;Woo, Seung-Hyun;Dubin, Adrienne E.;Moshourab, Rabih A.;Wetzel, Christiane;Petrus, Matt;Mathur, Jayanti;Begay, Valerie;Coste, Bertrand;Mainquist, James;Wilson, A. J.;Francisco, Allain G.;Reddy, Kritika;Qiu, Zhaozhu;Wood, John N.;Lewin, Gary R.;Patapoutian, Ardem
• 通讯作者: Patapoutian, Ardem

Mechanically Activated Ion Channels.

• DOI: 10.1016/j.neuron.2015.08.032
• 发表时间: 2015-09-23
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Ranade SS;Syeda R;Patapoutian A
• 通讯作者: Patapoutian A

Piezo2 senses airway stretch and mediates lung inflation-induced apnoea.

压电2感应气道拉伸并介导肺通胀引起的呼吸暂停。

• DOI: 10.1038/nature20793
• 发表时间: 2017-01-12
• 期刊: Nature
• 影响因子: 64.8
• 作者: Nonomura K;Woo SH;Chang RB;Gillich A;Qiu Z;Francisco AG;Ranade SS;Liberles SD;Patapoutian A
• 通讯作者: Patapoutian A

GPR68 Senses Flow and Is Essential for Vascular Physiology.

• DOI: 10.1016/j.cell.2018.03.076
• 发表时间: 2018-04-19
• 期刊: Cell
• 影响因子: 64.5
• 作者: Xu J;Mathur J;Vessières E;Hammack S;Nonomura K;Favre J;Grimaud L;Petrus M;Francisco A;Li J;Lee V;Xiang FL;Mainquist JK;Cahalan SM;Orth AP;Walker JR;Ma S;Lukacs V;Bordone L;Bandell M;Laffitte B;Xu Y;Chien S;Henrion D;Patapoutian A
• 通讯作者: Patapoutian A

Piezo2 is the principal mechanotransduction channel for proprioception.

• DOI: 10.1038/nn.4162
• 发表时间: 2015-12
• 期刊: Nature neuroscience
• 影响因子: 25
• 作者: Woo SH;Lukacs V;de Nooij JC;Zaytseva D;Criddle CR;Francisco A;Jessell TM;Wilkinson KA;Patapoutian A
• 通讯作者: Patapoutian A