Tbc1d15-17 Regulates Synaptic Development at the Drosophila Neuromuscular Junction
Tbc1d15-17 Regulates Synaptic Development at the Drosophila Neuromuscular Junction
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.
- Seoul National University Korea (Republic of)
- Sungshin Women's University Korea (Republic of)
GTPase-Activating Proteins, Molecular Sequence Data, Neuromuscular Junction, Presynaptic Terminals, rab7 GTP-Binding Proteins, Nerve Tissue Proteins, rab GTP-Binding Proteins, Gene Knockdown Techniques, Animals, Drosophila Proteins, Drosophila, Amino Acid Sequence, Sequence Alignment
GTPase-Activating Proteins, Molecular Sequence Data, Neuromuscular Junction, Presynaptic Terminals, rab7 GTP-Binding Proteins, Nerve Tissue Proteins, rab GTP-Binding Proteins, Gene Knockdown Techniques, Animals, Drosophila Proteins, Drosophila, Amino Acid Sequence, Sequence Alignment
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