KIF4 Motor Regulates Activity-Dependent Neuronal Survival by Suppressing PARP-1 Enzymatic Activity
| Autor: | Ryosuke Midorikawa, Nobutaka Hirokawa, Yosuke Takei |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Neurite
Cell Survival Recombinant Fusion Proteins Poly (ADP-Ribose) Polymerase-1 Kinesins Apoptosis Nerve Tissue Proteins Poly(ADP-ribose) Polymerase Inhibitors Biology General Biochemistry Genetics and Molecular Biology Mice Microtubule Ca2+/calmodulin-dependent protein kinase medicine Animals Growth Substances Cells Cultured Calcium signaling Neurons Biochemistry Genetics and Molecular Biology(all) Brain Depolarization Cell biology medicine.anatomical_structure Cytoplasm Calcium-Calmodulin-Dependent Protein Kinases Kinesin Calcium RNA Interference Calcium Channels Poly(ADP-ribose) Polymerases Calcium-Calmodulin-Dependent Protein Kinase Type 2 Nucleus |
| Zdroj: | Cell. 125:371-383 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2006.02.039 |
| Popis: | SummaryIn brain development, apoptosis is a physiological process that controls the final numbers of neurons. Here, we report that the activity-dependent prevention of apoptosis in juvenile neurons is regulated by kinesin superfamily protein 4 (KIF4), a microtubule-based molecular motor. The C-terminal domain of KIF4 is a module that suppresses the activity of poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme known to maintain cell homeostasis by repairing DNA and serving as a transcriptional regulator. When neurons are stimulated by membrane depolarization, calcium signaling mediated by CaMKII induces dissociation of KIF4 from PARP-1, resulting in upregulation of PARP-1 activity, which supports neuron survival. After dissociation from PARP-1, KIF4 enters into the cytoplasm from the nucleus and moves to the distal part of neurites in a microtubule-dependent manner. We suggested that KIF4 controls the activity-dependent survival of postmitotic neurons by regulating PARP-1 activity in brain development. |
| Databáze: | OpenAIRE |
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