Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells

被引：294

作者：

Rose, CR ^{[1
]}

Blum, R ^{[1
]}

Pichler, B ^{[1
]}

Lepier, A ^{[1
]}

Kafitz, KW ^{[1
]}

Konnerth, A ^{[1
]}

机构：

[1] Univ Munich, Inst Physiol, D-80336 Munich, Germany

来源：

NATURE | 2003年 / 426卷 / 6962期

关键词：

D O I：

10.1038/nature01983

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：

The neurotrophin receptor TrkB is essential for normal function of the mammalian brain(1-3). It is expressed in three splice variants. Full-length receptors (TrkB(FL)) possess an intracellular tyrosine kinase domain and are considered as those TrkB receptors that mediate the crucial effects of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT- 4/5). By contrast, truncated receptors (TrkB-T1 and TrkB-T2) lack tyrosine kinase activity and have not been reported to elicit rapid intracellular signalling(4). Here we show that astrocytes predominately express TrkB-T1 and respond to brief application of BDNF by releasing calcium from intracellular stores. The calcium transients are insensitive to the tyrosine kinase blocker K-252a and persist in mutant mice lacking TrkB(FL). By contrast, neurons produce rapid BDNF-evoked signals through TrkB(FL) and the Na(v)1.9 channel(5,6). Expression of antisense TrkB messenger RNA strongly reduces BDNF-evoked calcium signals in glia. Thus, our results show that, unexpectedly, TrkB-T1 has a direct signalling role in mediating inositol-1,4,5-trisphosphate-dependent calcium release; in addition, they identify a previously unknown mechanism of neurotrophin action in the brain.

引用

页码：74 / 78

页数：5

共 30 条

[11] Glia: Listening and talking to the synapse [J].