Congresos y reuniones científicas
Título:
Cellular mechanisms of activity dependent regulation of CPEB3 expression in mouse cerebellar stellate cells
Autor/es:
BARH K; BENDER C; LIU SQ
Reunión:
Jornada; Summer student meeting; 2012
Institución organizadora:
LSUHSC
Resumen:
Information
processing in the central nervous system is based on the balance of the actions
of excitatory and inhibitory neurons. Most excitatory neurons use glutamate as
their neurotransmitter. AMPA type glutamate receptors are essential for
moderating this excitatory synaptic transmission.The GluR2 subunit of AMPA
receptors (AMPARs) in cerebellar stellate cellsplay a key role in associative
learning and memory. A single fear-inducing stimulus causes an increase in
GluR2-containing AMPARs.? Cytoplasmic Polyadenylation Element Binding protein 3
(CPEB3) regulates GluR2 synthesis and is associated with learning and human
episodic memory. Preliminary study in our lab show that action potential (AP)
firing increasesCPEB3 expression and reduces synaptic GluR2 receptors.
Therefore, we examined the mechanism that regulates CPEB3 expression. We
investigated 1) the role of calcium entry via Voltage Gated Calcium Channels
(VGCC) during spontaneous acation potential firing; 2) its effect on protein
synthesis and protein degradation of CPEB3. Understanding the mechanism that
regulates CPEB3 expression helps in identifying mechanisms that regulates GluR2
and hence, the neuroplasticity associated to this receptor. Inhibition of
action potentials by TTX causes a significant decrease of ~25% in CPEB3 expression
in mouse cerebellar stellate cells. Membrane depolarization can activate
voltage gated calcium channels (VGCC). Here we found that blocking N-, T- and
L-type VGCCs,each causes a reduction in CPEB3 expression, and inhibition of all
three channels reduces the CPEB3 levels to that of TTX treatment. Thus
voltage-gated calcium channels play a key role in regulating CPEB3 expression.
The TTX-induced decrease in CPEB3 expression could result from an enhanced
protein degradation or suppression of synthesis of CPEB3 protein. Our
preliminary results show that MG132 completely prevents the TTX-induced
reduction in CPEB3 levels, indicating that inhibition of action potential
activity increases protein degradation of CPEB3 protein.