Amino acid sensing in hypothalamic tanycytes via umami taste receptors.
Amino acid sensing in hypothalamic tanycytes via umami taste receptors.
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DOI：
10.1016/j.molmet.2017.08.015
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发表时间：
2017-11
影响因子：
8.1
通讯作者：
Dale N
中科院分区：
文献类型：
--
作者：
Lazutkaite G;Soldà A;Lossow K;Meyerhof W;Dale N
下丘脑单细胞是排列在第三脑室壁并接触脑脊液 (CSF) 的神经胶质细胞。虽然已知它们可以检测脑脊液中的葡萄糖，但我们现在表明，单细胞还可以检测氨基酸，这是表示饱腹感的重要营养物质。 Ca2+ 成像和 ATP 生物传感用于检测单细胞对 l-氨基酸的反应。使用 ATP 受体拮抗剂和通道阻滞剂确定反应的下游途径。使用缺乏 Tas1r1 基因以及 mGluR4 受体拮抗剂的小鼠来表征受体。 Arg、Lys 和 Ala 等氨基酸会在单细胞中引发 Ca2+ 信号，并通过 pannexin 1 和 CalHM1 引发 ATP 释放，从而通过 P2 受体依赖性机制放大信号。缺乏 Tas1r1 基因的小鼠的单胞细胞对赖氨酸和精氨酸的反应减弱，但对丙氨酸的反应没有减弱。 mGluR4 拮抗剂大大降低了对丙氨酸和赖氨酸的反应。先前与味觉细胞有关的两种受体，Tas1r1/Tas1r3 异二聚体和 mGluR4，有助于脑脊液中的单胞体检测一系列氨基酸。下丘脑单细胞可以检测脑脊液中的氨基酸。该机制是味觉受体依赖性的。 Tas1r1/Tas1r3 介导对 L-精氨酸和 L-赖氨酸的反应。 mGluR4 介导对 L-丙氨酸的反应，部分介导对 L-赖氨酸的反应。由氨基酸引起的单胞的 ATP 释放到达弓状核。
Hypothalamic tanycytes are glial cells that line the wall of the third ventricle and contact the cerebrospinal fluid (CSF). While they are known to detect glucose in the CSF we now show that tanycytes also detect amino acids, important nutrients that signal satiety. Ca2+ imaging and ATP biosensing were used to detect tanycyte responses to l-amino acids. The downstream pathway of the responses was determined using ATP receptor antagonists and channel blockers. The receptors were characterized using mice lacking the Tas1r1 gene, as well as an mGluR4 receptor antagonist. Amino acids such as Arg, Lys, and Ala evoke Ca2+ signals in tanycytes and evoke the release of ATP via pannexin 1 and CalHM1, which amplifies the signal via a P2 receptor dependent mechanism. Tanycytes from mice lacking the Tas1r1 gene had diminished responses to lysine and arginine but not alanine. Antagonists of mGluR4 greatly reduced the responses to alanine and lysine. Two receptors previously implicated in taste cells, the Tas1r1/Tas1r3 heterodimer and mGluR4, contribute to the detection of a range of amino acids by tanycytes in CSF. Hypothalamic tanycytes can detect amino acids in cerebrospinal fluid. The mechanism is taste receptor-dependent. Tas1r1/Tas1r3 mediates responses to l-arginine and l-lysine. mGluR4 mediates responses to l-alanine and partially those of l-lysine. ATP release from tanycytes evoked by amino acids reaches into the arcuate nucleus.
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影响因子：
29
作者：
Blouet C;Schwartz GJ
通讯作者：
Schwartz GJ
影响因子：
29
作者：
Balland E;Dam J;Langlet F;Caron E;Steculorum S;Messina A;Rasika S;Falluel-Morel A;Anouar Y;Dehouck B;Trinquet E;Jockers R;Bouret SG;Prévot V
通讯作者：
Prévot V
影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
影响因子：
16.2
作者：
Elias, CF;Aschkenasi, C;Elmquist, JK
通讯作者：
Elmquist, JK
影响因子：
16.2
作者：
Cowley, MA;Smith, RG;Horvath, TL
通讯作者：
Horvath, TL