Reelin and stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment.
The Reelin ligand regulates a Dab1-dependent signaling pathway required for brain lamination and normal dendritogenesis, but the specific mechanisms underlying these actions remain unclear. We find that Stk25, a modifier of Reelin-Dab1 signaling, regulates Golgi morphology and neuronal polarization as part of an LKB1-Stk25-Golgi matrix protein 130 (GM130) signaling pathway. Overexpression of Stk25 induces Golgi condensation and multiple axons, both of which are rescued by Reelin treatment. Reelin stimulation of cultured neurons induces the extension of the Golgi into dendrites, which is suppressed by Stk25 overexpression. In vivo, Reelin and Dab1 are required for the normal extension of the Golgi apparatus into the apical dendrites of hippocampal and neocortical pyramidal neurons. This demonstrates that the balance between Reelin-Dab1 signaling and LKB1-Stk25-GM130 regulates Golgi dispersion, axon specification, and dendrite growth and provides insights into the importance of the Golgi apparatus for cell polarization.
Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Tohru
T
Matsuki
Russell T
RT
Matthews
Jonathan A
JA
Cooper
Marcel P
MP
van der Brug
Mark R
MR
Cookson
John A
JA
Hardy
Eric C
EC
Olson
Brian W
BW
Howell
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*; D000099317:Hippo Kinases
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D000091042:Reelin Protein; D012697:Serine Endopeptidases; C103773:Dab1 protein, mouse; C000717129:Reln protein, rat; C530661:Stk25 protein, mouse; D000099317:Hippo Kinases; C000717127:RELN protein, human; C000717128:Reln protein, mouse