RabGTPases as candidate mediators of SSR growth via Ral/Exocyst complex
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1
Center for Chronic Disease Studies (CEDOC), Portugal
Neuronal morphology is established during development but can subsequently be modified by synaptic activity, a process known as structural plasticity. Postsynaptic compartments, such as dendritic spines or postsynaptic membrane of the Drosophila neuromuscular junction (NMJ) (called the subsynaptic reticulum or SSR), are highly dynamic structures that grow during development and in response to activity. The shape of these structures is tightly coupled to synaptic function, but the mechanism underlying the establishment of the morphology and its relationship with functional plasticity are not well understood. One pathway that is known to be required for neuronal growth during development and in response to activity is the Ral/Exocyst pathway. Ral is a small GTPase that can bind to Exocyst, an octameric protein complex that tethers vesicles to the plasma membrane. Together, Ral and Exocyst, recruit vesicles to the postsynaptic membrane thereby contributing to SSR growth. However, the pathway by which Ral and the exocyst exert their functions is still elusive. Knowing 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 Drosophila Rab GTPases by two different approaches: 1) by screening a collection of YFP-tagged Rab GTPases locked in the constitutive active form for their capacity to mimic Ral- and exocyst-dependent effects on postsynaptic growth, and 2) to express Rab GTPases RNAi and in an active Ral background to test if Exocyst recruitment to SSR can be abolished. By systematically evaluating the localization of the Exocyst subunit Sec5 after postsynaptic activation, we identified some candidate Rab GTPases to mediate Ral/Exocyst effects. Altogether, this study contributes 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 with this pathway.
Acknowledgements
We thank Telmo Pereira from the Microscopy Facility for technical support. We thank Marta Santos and the Fly Facility; CONGENTO: consortium for genetically tractable organisms. This work was supported by H2020-GA661543-Neuronal Trafficking (ROT), IF/00392/2013/CP1192/CT0002, FCT – Portugal (ROT), CR - PD/BD/128340/2017 and by UID/Multi/04462/2013 from iNOVA4Health (co-funded by FCT-FEDER-PT2020),.
Keywords:
Drosophila melanogaster,
RabGTPases,
RalGTPase,
Subsynaptic reticulum (SSR),
exocyst complex
Conference:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.
Presentation Type:
Pitch communication + Poster presentation
Topic:
Cellular and Molecular Neurosciences
Citation:
Rodrigues
CP and
Teodoro
RO
(2019). RabGTPases as candidate mediators of SSR growth via Ral/Exocyst complex.
Front. Cell. Neurosci.
Conference Abstract:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019).
doi: 10.3389/conf.fncel.2019.01.00044
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Received:
21 Feb 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
PhD. Rita O Teodoro, Center for Chronic Disease Studies (CEDOC), Lisboa, Portugal, rita.o.teodoro@gmail.com