Anterograde Activin Signaling Regulates Postsynaptic Membrane Potential and GluRIIA/B Abundance at the Drosophila Neuromuscular Junction

Abstract

Members of the TGF-β superfamily play numerous roles in nervous system development and function. In Drosophila, retrograde BMP signaling at the neuromuscular junction (NMJ) is required presynaptically for proper synapse growth and neurotransmitter release. In this study, we analyzed whether the Activin branch of the TGF-β superfamily also contributes to NMJ development and function. We find that elimination of the Activin/TGF-β type I receptor babo, or its downstream signal transducer smox, does not affect presynaptic NMJ growth or evoked excitatory junctional potentials (EJPs), but instead results in a number of postsynaptic defects including depolarized membrane potential, small size and frequency of miniature excitatory junction potentials (mEJPs), and decreased synaptic densities of the glutamate receptors GluRIIA and B. The majority of the defective smox synaptic phenotypes were rescued by muscle-specific expression of a smox transgene. Furthermore, a mutation in actβ, an Activin-like ligand that is strongly expressed in motor neurons, phenocopies babo and smox loss-of-function alleles. Our results demonstrate that anterograde Activin/TGF-β signaling at the Drosophila NMJ is crucial for achieving normal abundance and localization of several important postsynaptic signaling molecules and for regulating postsynaptic membrane physiology. Together with the well-established presynaptic role of the retrograde BMP signaling, our findings indicate that the two branches of the TGF-β superfamily are differentially deployed on each side of the Drosophila NMJ synapse to regulate distinct aspects of its development and function.

Midgut-Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control

“…Consistent with previous results (Gibbens et al, 2011; Kim and O’Connor, 2014; Ting et al, 2007), we observed Actβ expression in the larval central neuron system (CNS), neuroendocrine cells, and motor neurons using Actβ-Gal4-driving GFP expression (Fig. S6A, C).…”

“…Actβ has been previously characterized as a neuronal factor and is abundantly expressed in the central and peripheral nervous systems (PNS) to modulate neuronal development and activity (Kim and O’Connor, 2014; Zhu et al, 2008). We demonstrate for the first time that Actβ is abundantly expressed in EEs of the larval midgut.…”

Activin signaling mediates muscle-to-adipose communication in a mitochondria dysfunction-associated obesity model

“…In addition to acting as a neuropeptide expressed in central or peripheral nerves (24,25), Actβ also acts as an endocrine peptide derived from enteroendocrine cells to target the fat body via the Babo receptor (14). Actβ is expressed at low levels in wild-type muscle (14); however, we observed a significant induction of Actβ expression when complex I was perturbed in muscle cells, suggesting that mitochondrial injury can turn on Actβ expression in the muscle to subsequently regulate fat body function.…”

DrosophilaActivin signaling promotes muscle growth through InR/dTORC1 dependent and independent processes

“…The w1118 strain was used as a wild-type (wt) control for babo, dSmad2 and ligand mutants. dSmad2F4, babofd4,babodf,Actβed80,daw1,daw11,myo1, and UAS-baboCA (constitutively active) lines have been described previously (Kim and O'Connor, 2014;Ting, et al, 2007;Brummel, et al, 1999). myoCR2 was generated by BestGene Inc by CRISPR-mediated mutagenesis using 5'-CTTCGACTATTCACCGCGCTATTA-3' as a guide RNA.…”