Abstract
The synaptic vesicle accumulation and subsequent morphological remodeling of axon terminals are characteristic features of presynaptic differentiation of zebrafish olfactory sensory neurons. The synaptic vesicle accumulation and axon terminal remodeling are regulated by protein kinase A and calcineurin signaling, respectively. To investigate upstream signals of presynaptic differentiation, we focused on Ca(2+) signaling as Ca(2+)/calmodulin is required for the activation of both calcineurin and some adenylyl cyclases. We here showed that application of Ca(2+)/calmodulin inhibitor or olfactory sensory neuron-specific expression of calmodulin inhibitory peptide suppressed both synaptic vesicle accumulation and axon terminal remodeling. Thus, the trigger of presynaptic differentiation could be Ca(2+) release from intracellular stores or Ca(2+) influx. Application of a phospholipase C inhibitor or olfactory sensory neuron-specific expression of inositol 1,4,5-trisphosphate (IP(3)) 5-phosphatase suppressed synaptic vesicle accumulation, but not morphological remodeling. In contrast, application of a voltage-gated Ca(2+) channel blocker or expression of Kir2.1 inward rectifying potassium channel prevented the morphological remodeling. We also provided evidence that IP(3) signaling acted upstream of protein kinase A signaling. Our results suggest that IP(3)-mediated Ca(2+)/calmodulin signaling stimulates synaptic vesicle accumulation and subsequent neuronal activity-dependent Ca(2+)/calmodulin signaling induces the morphological remodeling of axon terminals.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Analysis of Variance
-
Animals
-
Calcineurin / metabolism
-
Calcium / metabolism
-
Calcium Channel Blockers / pharmacology
-
Calcium Signaling / drug effects
-
Calcium Signaling / physiology*
-
Calmodulin / metabolism
-
Cyclic AMP-Dependent Protein Kinases / metabolism
-
Embryo, Nonmammalian
-
Enzyme Inhibitors / pharmacology
-
Gene Expression Regulation / drug effects
-
Green Fluorescent Proteins / genetics
-
Inositol Polyphosphate 5-Phosphatases
-
Microinjections
-
Olfactory Marker Protein / genetics
-
Olfactory Marker Protein / metabolism
-
Olfactory Pathways / cytology*
-
Olfactory Pathways / embryology
-
Olfactory Receptor Neurons
-
Phosphoric Monoester Hydrolases / metabolism
-
Potassium Channels, Inwardly Rectifying / genetics
-
Potassium Channels, Inwardly Rectifying / metabolism
-
Presynaptic Terminals / drug effects
-
Presynaptic Terminals / metabolism*
-
Synapses / drug effects
-
Synapses / physiology*
-
Synaptic Vesicles / drug effects
-
Synaptic Vesicles / physiology*
-
Transfection / methods
-
Type C Phospholipases / pharmacology
-
Vesicle-Associated Membrane Protein 2 / genetics
-
Vesicle-Associated Membrane Protein 2 / metabolism
-
Zebrafish
-
Zebrafish Proteins / genetics
-
Zebrafish Proteins / metabolism
Substances
-
Calcium Channel Blockers
-
Calmodulin
-
Enzyme Inhibitors
-
Kir2.1 channel
-
Olfactory Marker Protein
-
Potassium Channels, Inwardly Rectifying
-
Vesicle-Associated Membrane Protein 2
-
Zebrafish Proteins
-
enhanced green fluorescent protein
-
ompb protein, zebrafish
-
Green Fluorescent Proteins
-
Cyclic AMP-Dependent Protein Kinases
-
Calcineurin
-
Phosphoric Monoester Hydrolases
-
Inositol Polyphosphate 5-Phosphatases
-
Type C Phospholipases
-
Calcium