RRC ID 33700
Author Campbell DS, Okamoto H.
Title Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization.
Journal J. Cell Biol.
Abstract In addition to being critical for apoptosis, components of the apoptotic pathway, such as caspases, are involved in other physiological processes in many types of cells, including neurons. However, very little is known about their role in dynamic, nonphysically destructive processes, such as axonal arborization and synaptogenesis. We show that caspases were locally active in vivo at the branch points of young, dynamic retinal ganglion cell axonal arbors but not in the cell body or in stable mature arbors. Caspase activation, dependent on Caspase-3, Caspase-9, and p38 mitogen-activated protein kinase (MAPK), rapidly increased at branch points corresponding with branch tip addition. Time-lapse imaging revealed that knockdown of Caspase-3 and Caspase-9 led to more stable arbors and presynaptic sites. Genetic analysis showed that Caspase-3, Caspase-9, and p38 MAPK interacted with Slit1a-Robo2 signaling, suggesting that localized activation of caspases lie downstream of a ligand receptor system, acting as key promoters of axonal branch tip and synaptic dynamics to restrict arbor growth in vivo in the central nervous system.
Volume 203(4)
Pages 657-72
Published 2013-11-25
DOI 10.1083/jcb.201303072
PII jcb.201303072
PMID 24385488
PMC PMC3840933
MeSH Aging / metabolism Animals Axons / metabolism* Caspase 3 / metabolism* Caspase 9 / metabolism* Enzyme Activation / drug effects Gene Knockdown Techniques Morpholinos / pharmacology Nerve Tissue Proteins / metabolism* Presynaptic Terminals / drug effects Presynaptic Terminals / metabolism Protein Binding / drug effects Receptors, Immunologic / metabolism* Retinal Ganglion Cells / cytology Retinal Ganglion Cells / enzymology Signal Transduction* / drug effects Zebrafish / metabolism* Zebrafish Proteins / metabolism* p38 Mitogen-Activated Protein Kinases / metabolism
IF 8.784
Times Cited 22
Zebrafish RIKEN WT