Lee_2012_J.Neurosci_32_16296

Reference

Title : Learning-related synaptic growth mediated by internalization of Aplysia cell adhesion molecule is controlled by membrane phosphatidylinositol 4,5-bisphosphate synthetic pathway - Lee_2012_J.Neurosci_32_16296
Author(s) : Lee SH , Shim J , Choi SL , Lee N , Lee CH , Bailey CH , Kandel ER , Jang DJ , Kaang BK
Ref : Journal of Neuroscience , 32 :16296 , 2012
Abstract :

Long-term facilitation in Aplysia is accompanied by the growth of new synaptic connections between the sensory and motor neurons of the gill-withdrawal reflex. One of the initial steps leading to the growth of these synapses is the internalization, induced by 5-HT, of the transmembrane isoform of Aplysia cell-adhesion molecule (TM-apCAM) from the plasma membrane of sensory neurons (Bailey et al., 1992). However, the mechanisms that govern the internalization of TM-apCAM and how this internalization is coupled to the molecular events that initiate the structural changes are not fully understood. Here, we report that the synthesis of membrane phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)], which is known to be mediated by a signaling cascade through Aplysia Sec7 protein (ApSec7) and phosphatidylinositol-4-phosphate 5-kinase type I alpha (PIP5KIalpha) is required for both the internalization of TM-apCAM and the initiation of synaptic growth during 5-HT-induced long-term facilitation. Pharmacological blockade of PI(4,5)P(2) synthesis by the application of the inhibitor phenylarsine oxide blocked the internalization of apCAM. Furthermore, perturbation of the endogenous activation of ApSec7 and its downstream target PIP5KIalpha also blocked 5-HT-mediated internalization of TM-apCAM and synaptic growth. Finally, long-term facilitation was specifically impaired by blocking the ApSec7 signaling pathway at sensory-to-motor neuron synapses. These data indicate that the ApSec7/PIP5KIalpha signaling pathway is actively recruited during learning-related 5-HT signaling and acts as a key regulator of apCAM internalization associated with the formation of new synaptic connections during long-term facilitation.

PubMedSearch : Lee_2012_J.Neurosci_32_16296
PubMedID: 23152613

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Citations formats

Lee SH, Shim J, Choi SL, Lee N, Lee CH, Bailey CH, Kandel ER, Jang DJ, Kaang BK (2012)
Learning-related synaptic growth mediated by internalization of Aplysia cell adhesion molecule is controlled by membrane phosphatidylinositol 4,5-bisphosphate synthetic pathway
Journal of Neuroscience 32 :16296

Lee SH, Shim J, Choi SL, Lee N, Lee CH, Bailey CH, Kandel ER, Jang DJ, Kaang BK (2012)
Journal of Neuroscience 32 :16296