Neu1 sialidase and matrix metalloproteinase-9 cross-talk is essential for neurotrophin activation of Trk receptors and cellular signaling

作者：Jayanth Preethi; Amith Schammim Ray; Gee Katrina; Szewczuk Myron R^*

来源：Cellular Signalling, 2010, 22(8): 1193-1205.

DOI：10.1016/j.cellsig.2010.03.011

• Neu1 sialidase
• MMP-9
• Trk receptors
• Neurotrophin factors
• GPCR
• Trk-expressing cells
• Primary neurons

Neurotrophin-induced Trk tyrosine kinase receptor activation and neuronal cell survival responses have been reported to be under the control of a membrane associated sialidase. Here, we identify an unprecedented membrane sialidase mechanism initiated by nerve growth factor (NGF) binding to TrkA to potentiate GPCR-signaling via membrane God subunit proteins and matrix metalloproteinase-9 (MMP-9) activation to induce Neu1 sialidase activation in live primary neurons and TrkA- and TrkB-expressing cell lines. Central to this process is that Neul/MMP-9 complex is bound to TrkA on the cell surface of naive primary neurons and TrkA-expressing cells. Tamifiu completely blocks this sialidase activity in live TrkA-PC12 cells treated with NGF with an IC(50) of 3.876 mu M with subsequent inhibition of Trk activation in primary neurons and neurite outgrowth in TrkA-PC12 cells. Our findings uncover a Neu1 and MMP-9 cross-talk on the cell surface that is critically essential for neurotrophin-induced Trk tyrosine kinase receptor activation and cellular signaling.

• 出版日期2010-8