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Poster Full Abstracts - Neural Development
Poster board number is above title. The first author is the presenter
316
Institute of Genetics and Developmental Biology CAS, Beijing, China.
Synapses are highly specialized intercellular junctions that transmit information between neurons and their targets. Aberrant synapse morphology and
function underline a broad spectrum of neurological diseases. Therefore, the development and function of synapses have been under intensive studies for
several decades. Cyfip, also known as Sra-1, is first identified as a specific Rac1-associated protein. It is later shown to interact with the Fragile X mental
retardation protein FMRP, hence the name of Cyfip, cytoplasmic FMRP interacting protein. Cyfip is a component of the SCAR/WAVE complex that
activates Arp2/3 to initiate F-actin nucleation upon certain signals. Lack of
cyfip
results in dramatically shortened extension of neuromuscular junction
(NMJ) synapses with clustered and more numerous boutons. However, how Cyfip affects actin cytoskeleton and functions at synapses remains poorly
defined. We report here that Cyfip regulated the organization of F-actin structure in ovary and presynaptic NMJ terminals. Pharmacological and fluorescence
recovery after photobleaching (FRAP) assays showed that Cyfip suppressed F-actin assembly. Electron microscopy revealed a significant increase in
synaptic vesicle size in
cyfip
mutants. Consistently, the amplitudes of miniature excitatory junctional potentials were increased in
cyfip
mutants.
Furthermore, synaptic neurotransmission could not be maintained under high frequency stimulation, indicating a defect in endocytosis or replenishment of
synaptic vesicles in
cyfip
mutants. Additionally, reducing the dose of endocytic proteins by half dominantly enhanced
cyfip
mutant NMJ phenotypes. It is
known that up-regulation of BMP signaling (a major growth promoting pathway at
Drosophila
NMJ synapses) leads to the formation of satellite boutons in
endocytic mutants. As expected, we found an increased level of BMP signaling in
cyfip
mutants. Together, our data demonstrate for the first time that Cyfip
regulates synaptic growth and endocytosis by inhibiting F-actin assembly and suppressing BMP signaling.