Molecular Characterization of a Novel Intracellular ADP-Ribosyl Cyclase

被引：29

作者：

Churamani, Dev ^{[1
]}

Boulware, Michael J. ^{[2
]}

Geach, Timothy J. ^{[3
]}

Martin, Andrew C. R. ^{[4
]}

Moy, Gary W. ^{[5
]}

Su, Yi-Hsien ^{[5
]}

Vacquier, Victor D. ^{[5
]}

Marchant, Jonathan S. ^{[2
]}

Dale, Leslie ^{[3
]}

Patel, Sandip ^{[1
]}

机构：

[1] UCL, Dept Physiol, London, England

[2] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA

[3] UCL, Dept Anat & Dev Biol, London, England

[4] UCL, Dept Biochem & Mol Biol, London, England

[5] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 USA

来源：

PLOS ONE | 2007年 / 2卷 / 08期

基金：

英国生物技术与生命科学研究理事会; 美国国家科学基金会;

关键词：

D O I：

10.1371/journal.pone.0000797

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background. ADP-ribosyl cyclases are remarkable enzymes capable of catalyzing multiple reactions including the synthesis of the novel and potent intracellular calcium mobilizing messengers, cyclic ADP-ribose and NAADP. Not all ADP-ribosyl cyclases however have been characterized at the molecular level. Moreover, those that have are located predominately at the outer cell surface and thus away from their cytosolic substrates. Methodology/Principal Findings. Here we report the molecular cloning of a novel expanded family of ADP-ribosyl cyclases from the sea urchin, an extensively used model organism for the study of inositol trisphosphate-independent calcium mobilization. We provide evidence that one of the isoforms (SpARC1) is a soluble protein that is targeted exclusively to the endoplasmic reticulum lumen when heterologously expressed. Catalytic activity of the recombinant protein was readily demonstrable in crude cell homogenates, even under conditions where luminal continuity was maintained. Conclusions/Significance. Our data reveal a new intracellular location for ADP-ribosyl cyclases and suggest that production of calcium mobilizing messengers may be compartmentalized.

引用

页数：13

共 73 条

[1] Activation and inactivation of Ca2+ release by NAADP(+) [J].