Mutational Analysis of Rab3 Function for Controlling Active Zone Protein Composition at the Drosophila Neuromuscular Junction

PloS One
Shirui ChenEthan R Graf

Abstract

At synapses, the release of neurotransmitter is regulated by molecular machinery that aggregates at specialized presynaptic release sites termed active zones. The complement of active zone proteins at each site is a determinant of release efficacy and can be remodeled to alter synapse function. The small GTPase Rab3 was previously identified as playing a novel role that controls the distribution of active zone proteins to individual release sites at the Drosophila neuromuscular junction. Rab3 has been extensively studied for its role in the synaptic vesicle cycle; however, the mechanism by which Rab3 controls active zone development remains unknown. To explore this mechanism, we conducted a mutational analysis to determine the molecular and structural requirements of Rab3 function at Drosophila synapses. We find that GTP-binding is required for Rab3 to traffick to synapses and distribute active zone components across release sites. Conversely, the hydrolytic activity of Rab3 is unnecessary for this function. Through a structure-function analysis we identify specific residues within the effector-binding switch regions that are required for Rab3 function and determine that membrane attachment is essential. Our findings suggest th...Continue Reading

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Citations

May 6, 2016·Frontiers in Synaptic Neuroscience·Robert J Kittel, Manfred Heckmann
Sep 23, 2016·Frontiers in Cellular Neuroscience·Yao V ZhangTobias M Rasse
Apr 8, 2017·Current Opinion in Neurobiology·David Van Vactor, Stephan J Sigrist
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Methods Mentioned

BETA
GTPases
dissection
GTPase
nucleotide Exchange
transgenic

Software Mentioned

ELAVGeneswitch
ELAV
GeneSwitch
Patchmaster
MetaMorph
Igor Pro
Mini Analysis

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