ネトリン-1媒介のアクソン増殖とcAMP生成は,アデノシンA2b受容体との相互作用を必要とする

V Corset¹, K T Nguyen-Ba-Charvet, C Forcet

¹Laboratoire Apoptose et Différenciation, label La Ligue-Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 5534, Université Lyon 1, Villeurbanne, France.

Nature

|October 26, 2000

まとめ

軸索誘導に不可欠なネトリン-1は,受容体複合体を使用することがあります. 研究者らは,アデノシンA2b受容体がネトリン-1受容体として作用し,DCCと連携して軸索の成長を促進することを発見した.

科学分野:

神経科学は神経科学である.
分子生物学は分子生物学である.
細胞生物学細胞生物学

背景:

ネトリンは,軸索の延長と経路発見に不可欠な分泌タンパク質です.
大腸がん (DCC) で削除されたタンパク質は,間接的な証拠により,以前はネトリン-1受容体として示唆されていた.
以前の研究では,直接的なDCC-ネトリン-1相互作用が示されず,共受容体が必要であることを示唆していました.

研究の目的:

ネトリン-1シグナル伝達におけるDCCと他の膜タンパク質の相互作用を調査する.
軸索誘導に関与するネトリン-1の特定の受容体 (s) を特定する.
ネトリン-1媒介のアクソン増殖におけるアデノシンA2b受容体の役割を明らかにする.

主な方法:

DCCとアデノシンA2b受容体との相互作用を調査しました.
アデノシンA2b受容体がネトリン-1と結合し,cAMPの蓄積を誘発する能力を評価した.
ネトリン-1依存の背脊脊髄アクソン増殖におけるアデノシンA2b受容体の役割を調べました.

主要な成果:

DCCは,膜関連アデノシンA2b受容体と直接相互作用する.
アデノシンA2b受容体はネットリン-1と結合し,cAMPの蓄積を誘発する.
背脊脊髄ニューロンからのネットリン-1依存性アクソン外成長には,アデノシンA2b受容体が必要です.

結論:

アデノシンA2b受容体は,ネットリン-1受容体として機能する.
ネトリン-1の成長促進効果は,おそらくDCCとアデノシンA2b受容体の受容体複合体を含む.
この発見は,ニューロンの発達におけるネットリン-1シグナル伝達のための新しいメカニズムを明らかにしています.

さらに関連する動画

06:23

Visualizing Axonal Growth Cone Collapse and Early Amyloid β Effects in Cultured Mouse Neurons

Published on: October 30, 2018

07:53

Analyses of Actin Dynamics, Clutch Coupling and Traction Force for Growth Cone Advance

Published on: October 21, 2021

関連する概念動画

01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...

01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

01:27

Adrenergic Neurons: Neurotransmission

Postganglionic sympathetic fibers (except those supplying the sweat glands) releasing noradrenaline or norepinephrine are called noradrenergic or adrenergic neurons. Noradrenaline, dopamine, adrenaline, or epinephrine are collectively called "catecholamines" as they contain a catechol moiety and an amine side chain. The five stages of neurotransmitter release involve their synthesis, storage, release, reuptake and metabolism.
Synthesis: Catecholamine synthesis requires tyrosine, which is taken...

01:27

Adrenergic Receptors (Adrenoceptors): Classification

Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic...

01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...

01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...

関連する実験動画