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.
Schecterson
Leslayann C
LC
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA. lcs23@u.washington.edu
Hudson
Mark P
MP
Ko
Mabel
M
Philippidou
Polyxeni
P
Akmentin
Wendy
W
Wiley
Jesse
J
Rosenblum
Elise
E
Chao
Moses V
MV
Halegoua
Simon
S
Bothwell
Mark
M
D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D055571:Secretory Pathway / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D043562:Receptors, G-Protein-Coupled; D017475:Receptors, Nerve Growth Factor