Abstract
In 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology
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Brain / cytology
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Brain / growth & development
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Brain / physiology
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Calcium / metabolism
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Calcium Channels / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Survival*
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Cells, Cultured
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Growth Substances / metabolism
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Kinesins / genetics
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Kinesins / metabolism*
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Mice
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology
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Neurons / metabolism*
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerase Inhibitors*
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Poly(ADP-ribose) Polymerases / genetics
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Poly(ADP-ribose) Polymerases / metabolism*
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RNA Interference
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
Substances
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Calcium Channels
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Growth Substances
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Nerve Tissue Proteins
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Poly(ADP-ribose) Polymerase Inhibitors
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Recombinant Fusion Proteins
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Parp1 protein, mouse
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Kif4 protein, mouse
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Kinesins
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Calcium