Trk activation in the secretory pathway promotes Golgi fragmentation

Activation of nascent receptor tyrosine kinases within the secretory pathway has been reported, yet the consequences of intracellular activation are largely unexplored. We report that overexpression of the Trk neurotrophin receptors causes accumulation of autoactivated receptors in the ER-Golgi intermediate compartment. Autoactivated receptors exhibit inhibited Golgi-mediated processing and they inhibit Golgi-mediated processing of other co-expressed transmembrane proteins, apparently by inducing fragmentation of the Golgi apparatus. Signaling from G protein-coupled receptors is known to induce Trk transactivation. Transactivation of nascent TrkB in hippocampal neurons resulting from exposure to the neuropeptide PACAP caused Golgi fragmentation, whereas BDNF-dependent activation of TrkB did not. TrkB-mediated Golgi fragmentation employs a MEK-dependent signaling pathway resembling that implicated in regulation of Golgi fragmentation in mitotic cells. Neuronal Golgi fragments, in the form of dendritically localized Golgi outposts, are important determinants of dendritic growth and branching. The capacity of transactivated TrkB to enhance neuronal Golgi fragmentation may represent a novel mechanism regulating neural plasticity.