Abstract
The alteration of protein compositions at synapses
following receptor stimulation is a crucial event that is thought
to underlie processes such as memory storage and learning. However,
the mechanisms behind this regulation and the functional units
involved are not well known. Studies pointing to a group of
proteins encoded by mRNAs possessing cis-acting
elements that interact with mRNA binding proteins like the
cytoplasmic element binding protein (CPEB) provide us with
motivation to investigate the regulation of postsynaptic protein
subunits such as the α-subunit of
Ca2+/calmodulin-dependent protein kinase
(CaMKIIα) and the 2A subunit of
N-methyl-D-aspartate receptors (NR2A) after activation of glutamate
receptors. Based upon preliminary data from the Bassell Lab, we
hypothesize that the poly(A) polymerase Gld2 positively regulates
activity induced synthesis of CaMKIIα
and NR2A in dendrites and that chemical long-term
potentiation (LTP) stimulation will induce protein
synthesis-dependent insertion of NR2A in the plasma membrane. To
assess our propositions, we stimulated hippocampal neurons with
either glutamate or a chemical-LTP paradigm and observed the
effects of the stimulations on CaMKIIα
and NMDAR subunits through immunocytochemistry. Anisomycin, a
protein synthesis inhibitor, and Gld2 short hairpin RNA (shRNA)
lentiviruses were used to investigate the Gld2-dependent protein
synthesis of these subunits. From this study, we determined that
there is strong evidence suggesting glutamate stimulation increases
the Gld-2 dependent expression of CaMKIIα
and NR2A protein in distal dendritic regions. Although we did
not observe significant changes in the surface NMDAR subunit
expressions, we provide some suggestions for future experiments
that could better support the second part of our
hypothesis.
Table of Contents
Table of Contents
Introduction.......................................................................................................................1
Methods............................................................................................................................7
Results............................................................................................................................12
Discussion........................................................................................................................19
References.......................................................................................................................29
Figures............................................................................................................................32
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