The Role of Spartin-Interacting ProteinCG33129 in the Regulation of Synaptic Growth at theDrosophila Neuromuscular Junction

CG33129;neuromuscular junction;synaptic growth;retrograde signaling;Spartin;575

자연과학대학 협동과정유전공학전공 ;

University:서울대학교 대학원

关键词: CG33129;    neuromuscular junction;    synaptic growth;    retrograde signaling;    Spartin;    575;   

Others  :  http://s-space.snu.ac.kr/bitstream/10371/131155/1/000000008660.pdf

美国|英语

来源: Seoul National University Open Repository

【 摘 要 】

During development, synaptic morphology and plasticity rely on complex, bidirectional communication between presynaptic nerve terminals and postsynaptic target cells. A well-characterized retrograde signal that regulates synaptic growth in Drosophila melanogaster is Glass bottom boat (Gbb), a member of the bone morphogenic protein (BMP) family that is secreted from the postsynaptic muscle. Previous studies have shown that the hereditary spastic paraplegia (HSP) –related protein Spartin inhibits synapse growth by inducing BMP receptor endocytosis at the presynaptic terminals of Drosophila neuromuscular junctions (NMJ). The main objective of this thesis is to investigate the synaptic role of CG33129, a novel Spartin-interacting protein. Compared to wild type controls, CG33129 P-element mutants display synaptic overgrowth at the Drosophila NMJ. The knockdown of CG33129 presynaptically or postsynaptically using RNA interference leads to similar overgrowth. CG33129 mutations diminish the levels of a synaptic vesicle marker CSP and cell adhesion molecule FasII. CG33129 mutations also lead to the disruption of the tight association of the scaffolding proteins Dlg and Spectrin with the postsynaptic subsynaptic reticulum (SSR). Spectrin levels are increased and postsynaptic GluRIIA levels are reduced. Levels of phosphorylated Mad (P-Mad), a key BMP transcription factor, are remarkably increased in CG33129 mutants. Based on these findings, I suggest that CG33129 has important roles in the regulation of synaptic development.