Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila

Abstract

Semaphorins have been intensively studied for their role in dendritic and axonal pathfinding, but less is known about their potential role in synapse formation. In the adult giant fiber (GF) system of fruit flies (Drosophila melanogaster), we show that transmembrane Semaphorin 1a (Sema-1a) is involved in synapse formation in addition to its role in guidance during pathfinding. Cell-autonomous rescue experiments showed that Sema-1a is involved in assembly of a central synapse and that it is required both pre- and postsynaptically. We also found that pre- but not postsynaptic gain-of-function Sema-1a was able to disrupt the GF-motor neuron synapse and that the phenotype depended on a proline-rich intracellular domain that contains a putative Enabled binding site. We suggest that transmembrane Sema-1a is part of a bi-directional signaling system that leads to the formation of the GF synapse and possibly acts as both a ligand and a receptor.

Stereotyped Axon Pruning via Plexin Signaling Is Associated with Synaptic Complex Elimination in the Hippocampus

“…Sema3F Ϫ/Ϫ mice display a similar pruning defect in the IPB. Also consistent with the idea that plexin signaling from semaphorins was important for synapse elimination was the finding that invertebrate semaphorins serve as inhibitory signals for synapse formation in Drosophila (Matthes et al, 1995;Godenschwege et al, 2002), in which the loss of these signaling pathways results in promiscuous synapse formation.…”

Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot–Marie–Tooth neuropathy

“…Intracellular recordings from muscles of adult female flies were obtained following (33) with modification as described in ref. 34. In brief, the giant fibers were activated extracellularly in brain by 2 etched tungsten electrodes (one placed through each eye) using short pulses of 0.03 ms (Grass S44 stimulator, Grass Instruments).…”

The brain within the tumor: new roles for axon guidance molecules in cancers

“…Other transmembrane semaphorins were also suggested to act as receptors for instance Sema1a and Sema4D, in Drosophila embryo and in immune cells respectively. 75,76 Other class 6 semaphorins are able to inhibit axonal growth in dissociated neuronal culture [77][78][79] but their receptors are still unknown. There are several isoforms of SEMA6A and SEMA6B generated by alternative splicing.…”