| dc.description.abstract |
<p>The proper modification and trafficking of plasma membrane proteins are essential
for normal neuronal function, such as dendrite morphogenesis, spine formation and
synaptic plasticity. The secretory organelles including endoplasmic reticulum and
Golgi apparatus are critical for the trafficking of these molecules as shown in fibroblasts.
Although these secretory organelles have been observed in neurons including dendritic
branches, their spatial organization and function in protein trafficking, neuronal
development and plasticity are not clear yet. Here, I used photobleaching and photoactivation
approaches combined with electron microscopy to show that although rapidly diffusing
within the continuous network of the somato-dendritic ER, membrane proteins such as
nascent AMPA receptors are confined by ER spatial complexity. The spatial range of
ER membrane protein mobility becomes progressively confined over neuronal development
and is rapidly restricted by synaptic activity. Thus, constrained lateral mobility
within the ER provides a novel mechanism for compartmentalized trafficking of nascent
receptors throughout dendrites. I also identified an ER protein as a novel microtubule-associated
protein regulating dendritic ER spatial complexity, neuronal dendrite elongation and
spine formation. Together, these results describe the spatial organization of dendritic
ER and its role in regulating membrane protein trafficking, neuronal morphogenesis
and postsynaptic functions.</p>
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