Retrograde BMP signaling controls synaptic growth at the NMJ by regulating trio expression in motor neurons.
Retrograde signaling is essential for coordinating the growth of synaptic structures; however, it is not clear how it can lead to modulation of cytoskeletal dynamics and structural changes at presynaptic terminals. We show that loss of retrograde bone morphogenic protein (BMP) signaling at the Drosophila larval neuromuscular junction (NMJ) leads to a significant reduction in levels of Rac GEF Trio and a diminution of transcription at the trio locus. We further find that Trio is required in motor neurons for normal structural growth. Finally, we show that transgenic expression of Trio in motor neurons can partially restore NMJ defects in larvae mutant for BMP signaling. Based on our findings, we propose a model in which a retrograde BMP signal from the muscle modulates GTPase activity through transcriptional regulation of Rac GEF trio, thereby regulating the homeostasis of synaptic growth at the NMJ.
Ball
Robin W
RW
Department of Physiology, McGill University, Montréal, QC H3G 1Y6, Canada.
Warren-Paquin
Maude
M
Tsurudome
Kazuya
K
Liao
Edward H
EH
Elazzouzi
Fatima
F
Cavanagh
Chelsea
C
An
Beum-Soo
BS
Wang
Tian-Tian
TT
White
John H
JH
Haghighi
A Pejmun
AP
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis*; D006801:Humans; D009046:Motor Neurons / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; C490974:trio protein, Drosophila