PUBLICATION

Regulation of synaptic vesicle accumulation and axon terminal remodeling during synapse formation by distinct Ca signaling

Authors
Yoshida, T., Uchida, S., and Mishina, M.
ID
ZDB-PUB-090807-18
Date
2009
Source
Journal of neurochemistry   111(1): 160-170 (Journal)
Registered Authors
Mishina, Masayoshi, Yoshida, Tomoyuki
Keywords
axon terminal remodeling, Ca2+ signaling, inositol 1,4,5-trisphosphate, neuronal activity, presynaptic differentiation, synaptic vesicle
MeSH Terms
  • Calcineurin/metabolism
  • Embryo, Nonmammalian
  • Synapses/drug effects
  • Synapses/physiology*
  • Calcium/metabolism
  • Synaptic Vesicles/drug effects
  • Synaptic Vesicles/physiology*
  • Presynaptic Terminals/drug effects
  • Presynaptic Terminals/metabolism*
  • Calcium Channel Blockers/pharmacology
  • Phosphoric Monoester Hydrolases/metabolism
  • Green Fluorescent Proteins/genetics
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Microinjections
  • Transfection/methods
  • Potassium Channels, Inwardly Rectifying/genetics
  • Potassium Channels, Inwardly Rectifying/metabolism
  • Gene Expression Regulation/drug effects
  • Olfactory Pathways/cytology*
  • Olfactory Pathways/embryology
  • Analysis of Variance
  • Vesicle-Associated Membrane Protein 2/genetics
  • Vesicle-Associated Membrane Protein 2/metabolism
  • Olfactory Marker Protein/genetics
  • Olfactory Marker Protein/metabolism
  • Calcium Signaling/drug effects
  • Calcium Signaling/physiology*
  • Type C Phospholipases/pharmacology
  • Olfactory Receptor Neurons
  • Animals
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Calmodulin/metabolism
  • Enzyme Inhibitors/pharmacology
PubMed
19656262 Full text @ J. Neurochem.
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 (PKA) and calcineurin signaling, respectively. To investigate upstream signals of presynaptic differentiation, we focused on Ca(2+) signaling since 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 PKA 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.
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