當細胞體積出現(xiàn)大的變化時,，這對健康是不利的,。因此，我們的細胞都配備有能保持其體積不變的機制,。當周圍環(huán)境滲透壓發(fā)生變化,，能改變細胞體積時，細胞會檢測環(huán)境發(fā)生的變化,，細胞會調(diào)整其內(nèi)部的水分含量以應對這些影響,。這是通過專門的離子通道（離子運動）將水分排出或吸收進入細胞體內(nèi)來實現(xiàn)的。
然而,，是什么分子負責導致這一現(xiàn)象發(fā)生仍是未知的,。生理科學研究所、國家自然科學研究院副主席Yasunobu OKADA教授和他的研究小組已發(fā)現(xiàn)，能防止細胞因高滲條件而萎縮柄最終死亡（凋亡）的關鍵分子
滲透壓異常升高可能是由于如劇烈運動或鹽過多脫水等引起的,。他們所描述的分子是TRPM2的變種包含截斷的C端,。TRPM2是色氨酸家族成員之一，是與疼痛,、溫度,、壓力、味覺和視覺等感覺改變相關的離子通道,。
進一步研究發(fā)現(xiàn)TRPM2ΔC分子通過與CD38（循環(huán)ADP-核糖水解酶）結合而激活，CD38與II型糖尿病,、癌癥,、艾滋病病毒感染者和催產(chǎn)素的分泌等有關。
Yasunobu OKADA教授希望研究針對新發(fā)現(xiàn)的分子開展的研究為研究疾病打開了方便之門,，不僅有利于闡明疾病病理特點,，而且在未來還可能開發(fā)出潛在治療方法。（生物谷：Bioon）
doi:10.1113/jphysiol.2011.220947
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The ΔC splice-variant of TRPM2 is the hypertonicity-induced cation channel in HeLa cells, and the ecto-enzyme CD38 mediates its activation
Tomohiro Numata1,2,Kaori Sato1,Jens Christmann3,Romy Marx3,Yasuo Mori2,Yasunobu Okada1 andFrank Wehner1,3
Hypertonicity-induced cation channels (HICCs) are key-players in proliferation and apoptosis but their molecular correlate remains obscure. Furthermore, the activation profile of HICCs is not well defined yet. We report here that, in HeLa cells, intracellular adenosine diphosphate ribose (ADPr) and cyclic ADPr (cADPr), as supposed activators of TRPM2, elicited cation currents that were virtually identical to the osmotic activation of HICCs. Silencing of the expression of TRPM2 and of the ecto-enzyme CD38 (as a likely source of ADPr and cADPr) inhibited HICC as well as nucleotide-induced currents and, in parallel, the hypertonic volume response of cells (the regulatory volume increase, RVI) was attenuated. Quantification of intracellular cADPr levels and the systematic application of extra- vs. intracellular nucleotides indicate that the outwardly directed gradient rather than the cellular activity of ADPr and cADPr triggers TRPM2 activation, probably along with a simultaneous biotransformation of nucleotides. Cloning of TRPM2 identified the ΔC-splice variant as the molecular correlate of the HICC, which could be strongly supported by a direct comparison of the respective Ca2+ selectivity. Finally, immunoprecipitation and high-resolution FRET/FLIM imaging revealed the interaction of TRPM2 and CD38 in the native as well as in a heterologous (HEK293T) expression system. We propose transport-related nucleotide export via CD38 as a novel mechanism of TRPM2/HICC activation. With the biotransformation of nucleotides running in parallel, continuous zero trans-conditions are achieved which will render the system infinitely sensitive.
