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
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 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.
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
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
Minyeop Nahm, Sunyoung Park, Jihye Lee, and Seungbok Lee
Mol. Cells 2016; 39(10): 762-767 https://doi.org/10.14348/molcells.2016.0203