Drosophila neuromuscular synapse assembly and function require the TGF‐β type I receptor saxophone and the transcription factor Mad

Abstract

Transforming growth factor-betas (TGF-beta) comprise a superfamily of secreted proteins with diverse functions in patterning and cell division control. TGF-beta signaling has been implicated in synapse assembly and plasticity in both vertebrate and invertebrate systems. Recently, wishful thinking, a Drosophila gene that encodes a protein related to BMP type II receptors, has been shown to be required for the normal function and development of the neuromuscular junction (NMJ). These findings suggest that a TGF-beta-related ligand activates a signaling cascade involving type I and II receptors and the Smad family of transcription factors to orchestrate the assembly of the NMJ. Here we demonstrate that the TGF-beta type I receptor Saxophone and the downstream transcription factor Mothers against dpp (Mad) are essential for the normal structural and functional development of the Drosophila NMJ, a synapse that displays activity-dependent plasticity.

Cell Type-Specific Requirements for Heparan Sulfate Biosynthesis at the Drosophila Neuromuscular Junction: Effects on Synapse Function, Membrane Trafficking, and Mitochondrial Localization

“…Antibodies and immunohistochemistry. Third-instar larvae were dissected in ice-cold Ca 2ϩ -free HL-3 saline (70 mM NaCl, 5 mM KCl, 20 mM MgCl 2 , 10 mM NaHCO 3 , 5 mM trehalose, 100 mM sucrose, 5 mM HEPES, pH 7.2) (Rawson et al, 2003). Larvae were fixed with Bouin's fixative (70% picric acid, 25% 37% formaldehyde, 5% glacial acetic acid) for staining of NMJs with anti-Dally-like (30 min), anti-cytochrome c (5 min), and anti-glutamate receptor IIA (5 min).…”

“…Intracellular recordings were performed as described previously (Rawson et al, 2003) with minor modifications. Thin-walled glass intracellular electrodes were filled with 3 M KCl and had resistances of 10 -20 M⍀.…”

dCIP4 (Drosophila Cdc42-Interacting Protein 4) Restrains Synaptic Growth by Inhibiting the Secretion of the Retrograde Glass Bottom Boat Signal

“…At the Drosophila neuromuscular junction (NMJ), the bone morphogenetic protein (BMP) homolog Glass bottom boat (Gbb) acts as a muscle-derived retrograde signal that promotes synaptic growth and neurotransmitter release . This signal is conveyed into presynaptic neurons through a receptor complex consisting of the type-II receptor Wishful thinking (Wit) and either of two type-I receptors, Thickveins (Tkv) and Saxophone (Sax) (Aberle et al, 2002;Marques et al, 2002;Rawson et al, 2003). Receptor activation results in the phosphorylation of mothers against decapentaplegic (Mad).…”

The atypical cadherin flamingo regulates synaptogenesis and helps prevent axonal and synaptic degeneration in Drosophila

“…Other molecules are more directly involved in synaptogenesis, synaptic growth, or maintenance. These molecules include bone morphogenetic protein (Alberle et al, 2002;Marques et al, 2002;Rawson et al, 2003;McCabe et al, 2003;Keshishian and Kim, 2004), ubiquitin (Oh et al, 1994;DiAntonio et al, 2001;Murphey and Godenschwege, 2002;DiAntonio and Hicke, 2004), cell adhesion molecules (Washbourne et al, 2004), and Wingless signaling components (Packard et al, 2003;Charron and Tessier-Lavigne, 2005).…”