Neuron
Volume 41, Issue 6, 25 March 2004, Pages 891-905
Journal home page for Neuron

Article
Highwire Regulates Presynaptic BMP Signaling Essential for Synaptic Growth

https://doi.org/10.1016/S0896-6273(04)00073-XGet rights and content
Under an Elsevier user license
open archive

Abstract

Highwire (Hiw), a putative RING finger E3 ubiquitin ligase, negatively regulates synaptic growth at the neuromuscular junction (NMJ) in Drosophila. hiw mutants have dramatically larger synaptic size and increased numbers of synaptic boutons. Here we show that Hiw binds to the Smad protein Medea (Med). Med is part of a presynaptic bone morphogenetic protein (BMP) signaling cascade consisting of three receptor subunits, Wit, Tkv, and Sax, in addition to the Smad transcription factor Mad. When compared to wild-type, mutants of BMP signaling components have smaller NMJ size, reduced neurotransmitter release, and aberrant synaptic ultrastructure. BMP signaling mutants suppress the excessive synaptic growth in hiw mutants. Activation of BMP signaling, which in wild-type does not cause additional growth, in hiw mutants does lead to further synaptic expansion. These results reveal a balance between positive BMP signaling and negative regulation by Highwire, governing the growth of neuromuscular synapses.

Cited by (0)

3

These authors contributed equally to this work.

4

Present address: Max-Planck Institut, 35 D-72076 Tubingen, Germany.

5

Present address: Department of Anatomy, UCSF, Box 0452, San Francisco, California 94143.

6

Present address: Department of Cell Biology, University of Alabama, Birmingham, Alabama 35294.

7

Present address: Department of Biological Sciences, Florida Atlantic University, Boca Raton, Florida 33431.

8

Present address: Renovis, Inc., Two Corporate Drive, South San Francisco, California 94080.