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Dissecting the role of the Ral/Exocyst pathway in postsynaptic growth and activity-dependent plasticity
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Resumo(s)
Neurons are the most morphologically diverse cell type whose morphology determines many
functional aspects of a neuronal network. The primary shape of neurons is established during axon
and dendrite outgrowth and synapse formation, but can subsequently be modified by synaptic activity.
Postsynaptic compartments, such as dendritic spines or the postsynaptic membrane (called the
Subsynaptic Reticulum or SSR) of the Drosophila Neuromuscular Junction (NMJ) are highly dynamic
elements that are subject to this type of plasticity. The principal goal of this work is to define cellular
and molecular mechanisms of synaptic growth and plasticity. We focus on a novel pathway that
regulates neuronal morphology in response to activity through the engagement of Ral and the Exocyst
complex in the regulation of membrane growth at the synapse, in response to neuronal activity. Since
we know that Rab GTPases play a role in polarized vesicle delivery, we hypothesized that a subset of
them will be required to mediate Ral/Exocyst-dependent structural plasticity. Using the Drosophila
NMJ as a model synapse, we tested all Rab GTPases - by screening a collection of Rab GTPases
RNAi and YFP-tagged Rab GTPases - for their capacity to mimic Ral- and exocyst-dependent effects
on postsynaptic growth. We identified three candidate Rab GTPases that might mediate postsynaptic
growth in a Ral/Exocyst-dependent manner. Our main interest is to dissect the genetic cascade that
converts synaptic activity into postsynaptic membrane growth in a Ral/Exocyst-dependent manner,
and how Rab GTPases and its regulators/effectors interact and regulate this mechanism. We believe
that a deep understanding of the basic mechanisms and genes that regulate neuronal growth and
plasticity will serve to uncover general principles that link normal development and function to
dysfunction.
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Palavras-chave
Rab GTPases Drosophila Postsynapse Ral/Exocyst Neuronal Growth