Sequence, biochemical characterization, and developmental expression of a new member of the TGF-β superfamily in Drosophila melanogaster

The bone morphogenetic protein (BMP) ligand Glass bottom boat (Gbb) acts as a retrograde growth signal at the Drosophila neuromuscular junction (NMJ). Endocytic regulation of presynaptic BMP receptors has been proposed to attenuate retrograde BMP signaling. However, it remains unknown whether the Gbb signal is also regulated by postsynaptic mechanisms. Here, we provide evidence that Drosophila Cdc42-interacting protein 4 (dCIP4) functions postsynaptically to inhibit synaptic growth. dCIP4 is localized postsynaptically at NMJs. dcip4 mutations lead to synaptic overgrowth and increased presynaptic phosphorylated mothers against decapentaplegic (Mad) levels, and these defects are rescued by muscle-specific expression of dCIP4. Biochemical and genetic analyses demonstrate that dCIP4 acts downstream of Cdc42 to activate the postsynaptic Wsp-Arp2/3 pathway. We also show that BMP signaling is necessary for synaptic overgrowth in larvae lacking postsynaptic dcip4 or wsp. Finally, dCIP4 and Wsp inhibit Gbb secretion. Thus, we propose that dCIP4 restrains synaptic growth by inhibiting postsynaptic Gbb secretion through the Wsp-Arp2/3 pathway.

show abstract

“…8 D, available at www.jneurosci.org as supplemental material). Thus, the Gbb-GFP fusion protein was processed as expected (Doctor et al, 1992).…”

Section: Dcip4/wsp Inhibits Postsynaptic Gbb Secretionmentioning

confidence: 81%

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

Nahm

Kim²,

Paik³

et al. 2010

Journal of Neuroscience

View full text Add to dashboard Cite

show abstract

“…However, it will be interesting to explore whether the incomplete rescue does in fact reflect a necessary contribution from other tissues. Gbb is a secreted protein that is widely expressed, such as by the fat body, somatic and visceral muscle, neurohemal organs and ring gland (Ballard et al, 2009;Doctor et al, 1992;Marques et al, 2003), and may circulate in the hemolymph. Ongoing studies aim to determine whether tissues in addition to muscle are necessary, sufficient or act redundantly to modulate BMP signaling in CCAP-ENs.…”

Section: Retrograde Gbb Signaling Regulates Ccap Mip and Bursb In CCmentioning

confidence: 99%

Retrograde BMP signaling controls Drosophila behavior through regulation of a peptide hormone battery

Veverytsa

Allan

2011

Development

View full text Add to dashboard Cite

Retrograde BMP signaling in neurons plays conserved roles in synaptic efficacy and subtype-specific gene expression. However, a role for retrograde BMP signaling in the behavioral output of neuronal networks has not been established. Insect development proceeds through a series of stages punctuated by ecdysis, a complex patterned behavior coordinated by a dedicated neuronal network. In Drosophila, larval ecdysis sheds the old cuticle between larval stages, and pupal ecdysis everts the head and appendages to their adult external position during metamorphosis. Here, we found that mutants of the type II BMP receptor wit exhibited a defect in the timing of larval ecdysis and in the completion of pupal ecdysis. These phenotypes largely recapitulate those previously observed upon ablation of CCAP neurons, an integral subset of the ecdysis neuronal network. Here, we establish that retrograde BMP signaling in only the efferent subset of CCAP neurons (CCAP-ENs) is required to cell-autonomously upregulate expression of the peptide hormones CCAP, Mip and Bursicon β. In wit mutants, restoration of wit exclusively in CCAP neurons significantly rescued peptide hormone expression and ecdysis phenotypes. Moreover, combinatorial restoration of peptide hormone expression in CCAP neurons in wit mutants also significantly rescued wit ecdysis phenotypes. Collectively, our data demonstrate a novel role for retrograde BMP signaling in maintaining the behavioral output of a neuronal network and uncover the underlying cellular and gene regulatory substrates.

show abstract

“…Three of these, Dpp, Screw and Gbb, have been shown to transduce Bmp-type signals (Mad) and to use the type I receptors Tkv and Sax (Brummel et al, 1994;Haerry et al, 1998;Nguyen et al, 1998 (Doctor et al, 1992;Wharton et al, 1991), and can signal through Wit to regulate P-Mad accumulation in motoneurons and tissue culture cells (McCabe et al, 2003). As shown in Fig.…”

Section: Retrograde Gbb Signaling Is Required For Farp Expression In mentioning

confidence: 99%

Retrograde Gbb signaling through the Bmp type 2 receptor Wishful Thinking regulates systemic FMRFa expression inDrosophila

et al. 2003

View full text Add to dashboard Cite

Amidated neuropeptides of the FMRFamide class regulate numerous physiological processes including synaptic efficacy at the Drosophilaneuromuscular junction (NMJ). We demonstrate here that mutations in wishful thinking (wit) a gene encoding a DrosophilaBmp type 2 receptor that is required for proper neurotransmitter release at the neuromuscular junction, also eliminates expression of FMRFa in that subset of neuroendocrine cells (Tv neurons) which provide the systemic supply of FMRFa peptides. We show that Gbb, a Bmp ligand expressed in the neurohemal organ provides a retrograde signal that helps specify the peptidergic phenotype of the Tv neurons. Finally, we show that supplying FMRFa in neurosecretory cells partially rescues the witlethal phenotype without rescuing the primary morphological or electrophysiological defects of wit mutants. We propose that Wit and Gbb globally regulate NMJ function by controlling both the growth and transmitter release properties of the synapse as well as the expression of systemic modulators of NMJ synaptic activity.

show abstract

Sequence, biochemical characterization, and developmental expression of a new member of the TGF-β superfamily in Drosophila melanogaster

Cited by 103 publications

References 53 publications

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

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

Retrograde BMP signaling controls Drosophila behavior through regulation of a peptide hormone battery

Retrograde Gbb signaling through the Bmp type 2 receptor Wishful Thinking regulates systemic FMRFa expression inDrosophila

Contact Info

Product

Resources

About