Transactivation of Trk Neurotrophin Receptors by G-Protein-Coupled Receptor Ligands Occurs on Intracellular Membranes

• DOI: 10.1523/jneurosci.0010-04.2004
• Publication Date: 2004-07-28T19:57:48Z
• Authors: Rithwick Rajagopal; Zhe-Yu Chen; Francis S. Lee; Moses V. Chao
• Keywords: Trk receptor

Neurotrophins, such as NGF and BDNF, activate Trk receptor tyrosine kinases through dimerization at the cell surface followed by autophosphorylation intracellular signaling. It has been shown that activation of can also occur via a G-protein-coupled (GPCR) mechanism, without involvement neurotrophins. Two GPCR ligands, adenosine pituitary adenylate cyclase-activating polypeptide (PACAP), activity to increase survival neural cells stimulation Akt activity. To investigate mechanism transactivation, we have examined localization receptors in PC12 primary neurons after treatment with agonists PACAP. In contrast neurotrophin treatment, were sensitive transcriptional translational inhibitors, they found predominantly locations particularly associated Golgi membranes. Biotinylation immunostaining experiments confirm most transactivated are These results indicate there alternative modes activating absence binding signaling may persist inside neuronal cells.