BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission

Fiona P. Ukken, Joseph J. Bruckner, Kurt L. Weir, Sarah J. Hope, Samantha L. Sison, Ryan M. Birschbach, Lawrence J. Hicks, Kendra L. Taylor, Erik W. Dent, Graydon Bennett Gonsalvez, Kate M. O'Connor-Giles

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nervous wreck (Nwk) is a conserved F-BAR protein that attenuates synaptic growth and promotes synaptic function in Drosophila. In an effort to understand how Nwk carries out its dual roles, we isolated interacting proteins using mass spectrometry.We report a conserved interaction between Nwk proteins and BAR-SH3 sorting nexins, a family of membrane-binding proteins implicated in diverse intracellular trafficking processes. In mammalian cells, BAR-SH3 sorting nexins induce plasma membrane tubules that localize NWK2, consistent with a possible functional interaction during the early stages of endocytic trafficking. To study the role of BAR-SH3 sorting nexins in vivo, we took advantage of the lack of genetic redundancy in Drosophila and employed CRISPR-based genome engineering to generate null and endogenously tagged alleles of SH3PX1. SH3PX1 localizes to neuromuscular junctions where it regulates synaptic ultrastructure, but not synapse number. Consistently, neurotransmitter release was significantly diminished in SH3PX1 mutants. Double-mutant and tissue-specific-rescue experiments indicate that SH3PX1 promotes neurotransmitter release presynaptically, at least in part through functional interactions with Nwk, and might act to distinguish the roles of Nwk in regulating synaptic growth and function.

Original languageEnglish (US)
Pages (from-to)166-177
Number of pages12
JournalJournal of Cell Science
Volume129
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Sorting Nexins
Synaptic Transmission
Synapses
Drosophila
Neurotransmitter Agents
Clustered Regularly Interspaced Short Palindromic Repeats
Proteins
Neuromuscular Junction
Growth
Mass Spectrometry
Carrier Proteins
Membrane Proteins
Alleles
Cell Membrane
Genome

Keywords

  • Drosophila neuromuscular junction
  • Nervous wreck
  • Neurotransmission
  • Sorting nexin
  • Synaptogenesis

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ukken, F. P., Bruckner, J. J., Weir, K. L., Hope, S. J., Sison, S. L., Birschbach, R. M., ... O'Connor-Giles, K. M. (2016). BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission. Journal of Cell Science, 129(1), 166-177. https://doi.org/10.1242/jcs.178699

BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission. / Ukken, Fiona P.; Bruckner, Joseph J.; Weir, Kurt L.; Hope, Sarah J.; Sison, Samantha L.; Birschbach, Ryan M.; Hicks, Lawrence J.; Taylor, Kendra L.; Dent, Erik W.; Gonsalvez, Graydon Bennett; O'Connor-Giles, Kate M.

In: Journal of Cell Science, Vol. 129, No. 1, 01.01.2016, p. 166-177.

Research output: Contribution to journalArticle

Ukken, FP, Bruckner, JJ, Weir, KL, Hope, SJ, Sison, SL, Birschbach, RM, Hicks, LJ, Taylor, KL, Dent, EW, Gonsalvez, GB & O'Connor-Giles, KM 2016, 'BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission', Journal of Cell Science, vol. 129, no. 1, pp. 166-177. https://doi.org/10.1242/jcs.178699
Ukken, Fiona P. ; Bruckner, Joseph J. ; Weir, Kurt L. ; Hope, Sarah J. ; Sison, Samantha L. ; Birschbach, Ryan M. ; Hicks, Lawrence J. ; Taylor, Kendra L. ; Dent, Erik W. ; Gonsalvez, Graydon Bennett ; O'Connor-Giles, Kate M. / BAR-SH3 sorting nexins are conserved interacting proteins of Nervous wreck that organize synapses and promote neurotransmission. In: Journal of Cell Science. 2016 ; Vol. 129, No. 1. pp. 166-177.
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