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KMID : 0578320130360020163
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Molecules and Cells
2013 Volume.36 No. 2 p.163 ~ p.168
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Tbc1d15-17 Regulates Synaptic Development at the Drosophila Neuromuscular Junction
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Lee Min-Jung
Jang Soo-Yeon
Nahm Min-Yeop
Yoon Jin-Ho
Lee Seung-Bok
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Abstract
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Members of the Tre-2/Bub2/Cdc16 (TBC) family of proteins are believed to function as GTPase-activating proteins (GAPs) for Rab GTPases, which play pivotal roles in intracellular membrane trafficking. Although membrane trafficking is fundamental to neuronal morphogenesis and function, the roles of TBC-family Rab GAPs have been poorly characterized in the nervous system. In this paper, we provide genetic evidence that Tbc1d15?17, the Drosophila homolog of mammalian Rab7-GAP TBC1d15, is required for normal presynaptic growth and postsynaptic organization at the neuromuscular junction (NMJ). A loss-of-function mutation in Tbc1d15?17 or its presynaptic knockdown leads to an increase in synaptic bouton number and NMJ length. Tbc1d15?17 mutants are also defective in the distribution of the postsynaptic scaffold Discs-large (Dlg) and in the level of the postsynaptic glutamate subunit GluRIIA. These postsynaptic phenotypes are recapitulated by postsynaptic knockdown of Tbc1d15?17. We also show that presynaptic overexpression of a constitutively active Rab7 mutant in a wild-type background causes a synaptic overgrowth phenotype resembling that of Tbc1d15?17 mutants, while a dominant-negative form of Rab7 has the opposite effect. Together, our findings establish a novel role for Tbc1d15?17 and its potential substrate Rab7 in regulating synaptic development.
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KEYWORD
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Drosophila NMJ, postsynaptic organization, synaptic growth, Tbc1d15-17
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