Microtubule stabilizing effect of notch activation in primary cortical neurons.
The appropriate level of microtubule stability is fundamental in neurons to assure correct polarity, migration, vesicles transport and to prevent axonal degeneration. In the present study, we have identified Notch pathway as an endogenous microtubule stabilizer. Stimulation of Notch receptors by exposure of mouse cortical neurons to the Notch ligand Jagged1 resulted in increased microtubule stability, as measured by using antibodies against post-translationally modified alpha tubulin, and changes in axonal morphology and branching, with varicosity loss, thicker neurites and enlarged growth cones. Similar effects were found after exposure of the cells to different doses of Taxol. However, contrary to Taxol, Jagged1 induced downregulation of the microtubule severing protein Spastin. We suggest that a fine-tuned manipulation of Notch signaling may represent a novel approach to modulate neuronal cytoskeleton plasticity.
Ferrari-Toninelli
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Department of Biomedical Sciences and Biotechnologies, University of Brescia, viale Europa, 11, 25123 Brescia, Italy.
Bonini
S A
SA
Bettinsoli
P
P
Uberti
D
D
Memo
M
M
D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D008870:Microtubules / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology; D011099:Polyglutamic Acid / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051880:Receptors, Notch / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects; D000074181:Spastin; D014404:Tubulin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D014404:Tubulin; D011099:Polyglutamic Acid; D014443:Tyrosine; D012313:RNA; D053829:Amyloid Precursor Protein Secretases; D000251:Adenosine Triphosphatases; D000074181:Spastin; C498515:Spast protein, mouse; D017239:Paclitaxel