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Mol. Cells 2013; 36(2): 163-168

Published online August 31, 2013

https://doi.org/10.1007/s10059-013-0147-1

© The Korean Society for Molecular and Cellular Biology

Tbc1d15-17 Regulates Synaptic Development at the Drosophila Neuromuscular Junction

Min-Jung Lee, Sooyeon Jang, Minyeop Nahm, Jin-Ho Yoon, and Seungbok Lee

Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 1School of Biological Sciences and Chemistry, Sungshin Women’s University, Seoul 136-742, Korea

Received: May 13, 2013; Accepted: May 23, 2013

Abstract

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 lossof-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.

Keywords Drosophila NMJ, postsynaptic organization, synaptic growth, Tbc1d15-17

Article

Research Article

Mol. Cells 2013; 36(2): 163-168

Published online August 31, 2013 https://doi.org/10.1007/s10059-013-0147-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Tbc1d15-17 Regulates Synaptic Development at the Drosophila Neuromuscular Junction

Min-Jung Lee, Sooyeon Jang, Minyeop Nahm, Jin-Ho Yoon, and Seungbok Lee

Department of Cell and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 110-749, Korea, 1School of Biological Sciences and Chemistry, Sungshin Women’s University, Seoul 136-742, Korea

Received: May 13, 2013; Accepted: May 23, 2013

Abstract

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 lossof-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.

Keywords: Drosophila NMJ, postsynaptic organization, synaptic growth, Tbc1d15-17

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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