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

Published online June 27, 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
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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