Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor
Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor
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DOI：
10.1096/fj.09-153601
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发表时间：
2010-09-01
期刊：
影响因子：
4.8
通讯作者：
Di Virgilio, Francesco
中科院分区：
文献类型：
--
作者：
Adinolfi, Elena;Cirillo, Maria;Di Virgilio, Francesco
P2X7是嘌呤能受体P2X亚家族中最大的成员。一个典型的特征是羧基尾部，它允许形成大孔。最近，已经鉴定了天然存在的截短的P2 X7剪接变体，同种型B（P2 X7 B）。在这里，我们表明，在HEK293细胞，缺乏内源性P2X受体的细胞类型，P2X7B的表达介导ATP刺激的通道活性，但不质膜透化，提高内质网Ca（2+）含量，激活转录因子NFATc1，增加细胞ATP含量，并刺激生长。此外，转染P2X7B的HEK293细胞（HEK293-P2X7B）与大多数肿瘤细胞一样，显示出较强的软琼脂浸润能力。当与全长P2X7（P2X7A）共表达时，P2X7B与P2X7A共组装成异源三聚体，并增强由后一种受体介导的所有已知反应。P2X7B mRNA在人体组织中广泛分布，尤其是在免疫系统和神经系统中，其表达水平远高于P2X7A。最后，P2X7B的表达在外周血淋巴细胞的促有丝分裂刺激中增加。总而言之，这些数据表明P2X7B在几种人体组织中广泛表达，调节P2X7A功能，参与控制细胞生长，并可能有助于理解P2X7受体在控制正常和癌细胞增殖中的作用。Adinolfi，E.，Cirillo，M.，Woltersdorf，R.，Falzoni，S.，Chiozzi，P.，Pellegatti，P.，卡莱加里湾G.的，Sandona，D.，Markwardt，F.，Schmalzing，G.，Dianzilio，F. P2X7受体的天然存在的截短同种型的营养活性。FASEB J.24，3393 - 3404（2010）。www.fasebj.org
P2X7 is the largest member of the P2X subfamily of purinergic receptors. A typical feature is the carboxyl tail, which allows formation of a large pore. Recently a naturally occurring truncated P2X7 splice variant, isoform B (P2X7B), has been identified. Here we show that P2X7B expression in HEK293 cells, a cell type lacking endogenous P2X receptors, mediated ATP-stimulated channel activity but not plasma membrane permeabilization, raised endoplasmic reticulum Ca(2+) content, activated the transcription factor NFATc1, increased the cellular ATP content, and stimulated growth. In addition, P2X7B-transfected HEK293 cells (HEK293-P2X7B), like most tumor cells, showed strong soft agar-infiltrating ability. When coexpressed with full-length P2X7 (P2X7A), P2X7B coassembled with P2X7A into a heterotrimer and potentiated all known responses mediated by this latter receptor. P2X7B mRNA was found to be widely distributed in human tissues, especially in the immune and nervous systems, and to a much higher level than P2X7A. Finally, P2X7B expression was increased on mitogenic stimulation of peripheral blood lymphocyte. Altogether, these data show that P2X7B is widely expressed in several human tissues, modulates P2X7A functions, participates in the control of cell growth, and may help understand the role of the P2X7 receptor in the control of normal and cancer cell proliferation.-Adinolfi, E., Cirillo, M., Woltersdorf, R., Falzoni, S., Chiozzi, P., Pellegatti, P., Callegari, M. G., Sandona, D., Markwardt, F., Schmalzing, G., Di Virgilio, F. Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J. 24, 3393-3404 (2010). www.fasebj.org