Tbc1d15-17 regulates synaptic development at the Drosophila neuromuscular junction. 2013

Min-Jung Lee, and Sooyeon Jang, and Minyeop Nahm, and 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.

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.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D004330 Drosophila A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. Fruit Fly, Drosophila,Drosophila Fruit Flies,Drosophila Fruit Fly,Drosophilas,Flies, Drosophila Fruit,Fly, Drosophila Fruit,Fruit Flies, Drosophila
D000090802 rab7 GTP-Binding Proteins A small family of rab GTP-binding proteins that play a key role in membrane trafficking in the late endocytic and autophagic pathways. Rab7 Proteins,ras-Related Protein Rab-7,GTP-Binding Proteins, rab7,Protein Rab-7, ras-Related,Proteins, Rab7,Proteins, rab7 GTP-Binding,Rab-7, ras-Related Protein,rab7 GTP Binding Proteins,ras Related Protein Rab 7
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016415 Sequence Alignment The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations
D017729 Presynaptic Terminals The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. Axon Terminals,Nerve Endings, Presynaptic,Synaptic Boutons,Synaptic Terminals,Axon Terminal,Bouton, Synaptic,Boutons, Synaptic,Ending, Presynaptic Nerve,Endings, Presynaptic Nerve,Nerve Ending, Presynaptic,Presynaptic Nerve Ending,Presynaptic Nerve Endings,Presynaptic Terminal,Synaptic Bouton,Synaptic Terminal,Terminal, Axon,Terminal, Presynaptic,Terminal, Synaptic,Terminals, Axon,Terminals, Presynaptic,Terminals, Synaptic
D055785 Gene Knockdown Techniques The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES. Gene Knock Down Techniques,Gene Knock Down,Gene Knock-Down,Gene Knock-Down Techniques,Gene Knockdown,Gene Knock Downs,Gene Knock-Down Technique,Gene Knock-Downs,Gene Knockdown Technique,Gene Knockdowns,Knock Down, Gene,Knock Downs, Gene,Knock-Down Technique, Gene,Knock-Down Techniques, Gene,Knock-Down, Gene,Knock-Downs, Gene,Knockdown Technique, Gene,Knockdown Techniques, Gene,Knockdown, Gene,Knockdowns, Gene,Technique, Gene Knock-Down,Technique, Gene Knockdown,Techniques, Gene Knock-Down,Techniques, Gene Knockdown

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