Trk receptors need neutral sphingomyelinase activity to promote cell viability. Issue 1 (5th December 2013)

• Record Type: Journal Article
• Authors: Candalija, Ana; Cubí, Roger; Ortega, Arturo; Aguilera, José; Gil, Carles
• Is Part Of: FEBS letters. Volume 588:Issue 1(2014)
• Page Start: 167
• Page End: 174
• Publication Date: 2013-12-05
• Subjects: BDNF -- Brain-Derived Neurotrophic Factor -- Cer -- ceramide -- CGN -- cultured granule neurons -- MTT -- 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- NGF -- Nerve Growth Factor -- nSMase -- neutral sphingomyelinase -- NT -- neurotrophins -- SM -- sphingomyelin -- SphK -- sphingosine kinase -- Neurotrophin -- Sphingomyelinase -- Ceramide -- Phosphorylation -- Granule neuron -- PC12; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.11.032
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Neurotrophins are a group of secreted polypeptides, which comprises Nerve Growth Factor (NGF) and Brain‐Derived Neurotrophic Factor (BDNF). Each neurotrophin can bind specifically to a tyrosine kinase Trk receptor (TrkA, TrkB or TrkC), while all of the neurotrophins can bind, with similar affinity, to the p75 neurotrophin receptor (p75 NTR ). Experiments on cell viability promotion by BDNF in granule neurons or by NGF in PC12 cells show that neurotrophin‐exerted cell viability is neutral sphingomyelinase (nSMase)‐dependent, since GW4869 or siRNA knockdown abrogates the protective effects, as well as neurotrophin‐induced Akt phosphorylation. Finally, the assessment of nSMase activity promotion drives to the conclusion that neurotrophins can promote cell viability through Trk receptors in a manner depending on basal nSMase but not through SMase activity enhancement. Abstract : The role of neutral sphingomyelinase activity in neurotrophin‐promoted cell viability is studied. Sphingomyelinase activity is essential in the BDNF‐induced Akt phosphorylation. Neurotrophins do not promote neutral sphingomyelinase activity by Trk receptors. Neurotrophins need basal neutral sphingomyelinase to promote cell viability.