@article{9ccde4a74ccf4158b17dc9fe25c5da40,
title = "Truncated TrkB-T1 mediates neurotrophin-evoked calcium signalling in glia cells",
abstract = "The neurotrophin receptor TrkB is essential for normal function of the mammalian brain. It is expressed in three splice variants. Full-length receptors (TrkBFL) 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. 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 TrkBFL. By contrast, neurons produce rapid BDNF-evoked signals through TrkBFLand the Nav1.9 channel. 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.",
author = "Rose, {Christine R.} and Robert Blum and Bruno Pichler and Alexandra Lepier and Kafitz, {Karl W.} and Arthur Konnerth",
note = "Funding Information: Acknowledgements We thank A. Donald for help with sperm counting, and A. MacColl for statistical advice. T.P. was supported by a scholarship from the Swedish University of Agricultural Sciences and a grant from the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); T.R.B. by a grant from the Natural Research Council (NERC); C.K.C. by a studentship from NERC (to T.R.B.); and H.L. by a studentship from the Zoology Department of Stockholm University. T.R.B. and T.P. developed the sperm collection technique; T.P. designed the female promiscuity and female novelty experiments, and together with C.K.C. and H.L. carried them out; C.K.C. designed the female quality experiment with T.R.B. and carried it out together with H.L.; C.K.C. analysed the data with T.P.; T.P. wrote the paper; S.J. helped with field work and the provision of research facilities. Funding Information: Acknowledgements We thank H. Thoenen for critically discussing the manuscript; T. Hunter for the TrkB cDNA isoforms; J.-i. Miyazaki for pCAGGS and pCAGGS–eGFP; M. Meyer for help with the knockout mice; and I. Schneider, R. Maul and I. M{\"u}hlhahn for technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft (to C.R.R. and A.K.).",
year = "2003",
month = nov,
day = "6",
doi = "10.1038/nature01983",
language = "English",
volume = "426",
pages = "74--78",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "6962",
}