Tbc1d15-17 regulates synaptic development at the Drosophila neuromuscular junction

Mol Cells. 2013 Aug;36(2):163-8. doi: 10.1007/s10059-013-0147-1. Epub 2013 Jun 27.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / physiology*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Knockdown Techniques
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / physiology*
  • Presynaptic Terminals / physiology*
  • Sequence Alignment
  • rab GTP-Binding Proteins / metabolism
  • rab7 GTP-Binding Proteins

Substances

  • Drosophila Proteins
  • GTPase-Activating Proteins
  • Nerve Tissue Proteins
  • Tbc1d15-17 protein, Drosophila
  • rab7 GTP-Binding Proteins
  • rab GTP-Binding Proteins