來自九所研究機(jī)構(gòu)的科學(xué)家們通過跨學(xué)科合作，明確了我們感知甜味,、苦味和鮮味的路徑,。他們發(fā)現(xiàn)，味覺感受細(xì)胞中的蛋白CALHM1（calcium homeostasis modulator 1）,，是感知甜味,、苦味和鮮味時必不可少的新型離子通道。ATP經(jīng)由這一通道離開味覺細(xì)胞,，并將味覺信息傳遞到腦部,。文章發(fā)表在本期的《自然》（Nature）雜志上。
味蕾具有特化的味覺細(xì)胞,，這些細(xì)胞中的受體與味覺分子結(jié)合,，會在細(xì)胞內(nèi)啟動一系列復(fù)雜的分子事件?？茖W(xué)家們已經(jīng)知道,，當(dāng)甜味、苦味和鮮味分子接觸舌頭時,，會激活I(lǐng)I型味覺細(xì)胞中的味覺受體,。但人們并不了解這些味覺細(xì)胞將味覺信息傳遞到腦部的機(jī)制。這也是味覺感知路徑中缺失的一環(huán),。
現(xiàn)在,，研究人員終于闡明了感知甜味、苦味和鮮味的最后一步,。他們發(fā)現(xiàn),，CALHM1通道蛋白位于味覺細(xì)胞的外膜,，負(fù)責(zé)控制離子和分子的進(jìn)出。在感知甜味,、苦味和鮮味的味覺細(xì)胞中,，細(xì)胞膜上CALHM1形成的通道打開，讓作為神經(jīng)遞質(zhì)的ATP分子離開,，向相鄰神經(jīng)元傳遞信號,，最終將味覺信息輸送到大腦內(nèi)相應(yīng)的感知區(qū)域。（ATP分子是機(jī)體內(nèi)的主要能源,。）研究顯示,，CALHM1基因只在II型味覺細(xì)胞中特異性表達(dá)，也就是說該蛋白只存在于感知甜味,、苦味和鮮味的細(xì)胞中,。
研究人員在小鼠模型中敲除了Calhm1基因，發(fā)現(xiàn)缺乏Calhm1通道蛋白的小鼠無法釋放ATP來給大腦傳遞甜味,、苦味和鮮味的信息,。和人類一樣，具有CALHM1基因的小鼠更喜歡甜味,，回避苦味,。但缺乏CALHM1的小鼠則不同，甜味和苦味對它們來說就和白水沒什么兩樣,，它們完全沒有品嘗到味道,。不過，研究人員指出,，該基因缺失并沒有影響小鼠對鹽味和酸味的感知,，因為這兩種味道的感知是由其他味覺細(xì)胞介導(dǎo)的。
此前人們曾認(rèn)為,，通道蛋白pannexin和connexin也參與了味覺細(xì)胞的ATP釋放,。但這項新研究顯示這兩種蛋白并不是必須的，由此推翻了人們之前的推測,。
這項研究展示了一個具有明確生理功能的ATP離子通道,，不僅闡明了CALHM1在甜味、苦味和鮮味感知中的關(guān)鍵作用,，也為該蛋白在其他組織中的功能帶來了啟示,。文章指出，CALHM1最初被認(rèn)為負(fù)責(zé)控制細(xì)胞內(nèi)的鈣離子水平,，現(xiàn)在它很可能還在大腦等區(qū)域參與了ATP介導(dǎo)的細(xì)胞間通訊,。(生物谷Bioon.com)
doi:10.1038/nature11906
PMC:
PMID:
CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes
Akiyuki Taruno, Valérie Vingtdeux, Makoto Ohmoto, Zhongming Ma, Gennady Dvoryanchikov, Ang Li, Leslie Adrien
Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of ATP, which acts as a neurotransmitter to activate afferent neural gustatory pathways1. However, how ATP is released to fulfil this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel2, 3, is indispensable for taste-stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas their recognition of sour and salty tastes remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type?II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type?II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Thus, CALHM1 is a voltage-gated ATP-release channel required for sweet, bitter and umami taste perception.
