專題：Nature報導
近期的Nature在線版發表了俄亥俄州大學神經分子科學研究中心，牛津大學，愛丁堡大學，北京大學等多國研究人員參與的文章，NAADP mobilizes calcium from acidic organelles through two-pore channels。
在哺乳動物的細胞中Ca2+離子的流動會導致重要的信號轉導過程產生，一般這一過程受inositol-1,4,5-trisphosphate (InsP3), cyclic ADP ribose 和 nicotinic acid adenine dinucleotide phosphate (NAADP)調控。InsP3和cyclic ADP ribose能與相對應的受體結合促進內質網釋放Ca2+離子。相反，胞內儲存Ca+2的過程受NAADP的調控，然而，目前學界對NAADP的受體的鑑定存在不同的意見。
在本研究中，研究小組發現一個雙孔的通道（two-pore channels，TPCs）可能是NAADP受體家族的成員，人類的TPC1（也稱TPCN1）和雞的TPC3（TPCN3）在內涵體膜上表達，在人類的HEK293細胞中，人類的TCP2僅在溶酶體膜上表達。聚集大量TPC2的膜具有高度的NAADP的親和性。
研究結果表明，NAADP的TPCs模式的受體具有誘導酸性細胞器釋放Ca2+的功效。這些研究成果有助了解Ca2+通道和信號轉導，有助人們了解NAADP的作用模式。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 22 April 2009 | doi:10.1038/nature08030
NAADP mobilizes calcium from acidic organelles through two-pore channels
Peter J. Calcraft1,7, Margarida Ruas2,7, Zui Pan3,7, Xiaotong Cheng2, Abdelilah Arredouani2, Xuemei Hao4,5, Jisen Tang5, Katja Rietdorf2, Lydia Teboul6, Kai-Ting Chuang2, Peihui Lin3, Rui Xiao5, Chunbo Wang5, Yingmin Zhu5, Yakang Lin5, Christopher N. Wyatt1, John Parrington2, Jianjie Ma3, A. Mark Evans1, Antony Galione2 & Michael X. Zhu5
1 Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, Scotland, UK
2 Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
3 Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA
4 College of Life Sciences, Peking University, Beijing 100871, China
5 Department of Neuroscience, Biochemistry, and Center for Molecular Neurobiology, The Ohio State University, 1060 Carmack Road, Columbus, Ohio 43210, USA
6 The Mary Lyon Centre, MRC Harwell, Oxfordshire OX11 0RD, UK
7 These authors contributed equally to this work.
Ca2+ mobilization from intracellular stores represents an important cell signalling process1 that is regulated, in mammalian cells, by inositol-1,4,5-trisphosphate (InsP3), cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). InsP3 and cyclic ADP ribose cause the release of Ca2+ from sarcoplasmic/endoplasmic reticulum stores by the activation of InsP3 and ryanodine receptors (InsP3Rs and RyRs). In contrast, the nature of the intracellular stores targeted by NAADP and the molecular identity of the NAADP receptors remain controversial1, 2, although evidence indicates that NAADP mobilizes Ca2+ from lysosome-related acidic compartments3, 4. Here we show that two-pore channels (TPCs) comprise a family of NAADP receptors, with human TPC1 (also known as TPCN1) and chicken TPC3 (TPCN3) being expressed on endosomal membranes, and human TPC2 (TPCN2) on lysosomal membranes when expressed in HEK293 cells. Membranes enriched with TPC2 show high affinity NAADP binding, and TPC2 underpins NAADP-induced Ca2+ release from lysosome-related stores that is subsequently amplified by Ca2+-induced Ca2+ release by InsP3Rs. Responses to NAADP were abolished by disrupting the lysosomal proton gradient and by ablating TPC2 expression, but were only attenuated by depleting endoplasmic reticulum Ca2+ stores or by blocking InsP3Rs. Thus, TPCs form NAADP receptors that release Ca2+ from acidic organelles, which can trigger further Ca2+ signals via sarcoplasmic/endoplasmic reticulum. TPCs therefore provide new insights into the regulation and organization of Ca2+ signals in animal cells, and will advance our understanding of the physiological role of NAADP.