Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic

James E C Jepson, Mohammed Shahidullah, Die Liu, Sylvain J. le Marchand, Sha Liu, Mark Wu, Irwin B. Levitan, Matthew B. Dalva, Kyunghee Koh

Research output: Contribution to journalArticle

Abstract

Synaptic scaffold proteins control the localization of ion channels and receptors, and facilitate molecular associations between signaling components that modulate synaptic transmission and plasticity. Here, we define novel roles for a recently described scaffold protein, Dsychronic (DYSC), at the Drosophila larval neuromuscular junction. DYSC is the Drosophila homolog of whirlin/DFNB31, a PDZ domain protein linked to Usher syndrome, the most common form of human deaf-blindness. We show that DYSC is expressed presynaptically and is often localized adjacent to the active zone, the site of neurotransmitter release. Loss of DYSC results in marked alterations in synaptic morphology and cytoskeletal organization. Moreover, active zones are frequently enlarged and misshapen in dysc mutants. Electrophysiological analyses further demonstrate that dysc mutants exhibit substantial increases in both evoked and spontaneous synaptic transmission. We have previously shown that DYSC binds to and regulates the expression of the Slowpoke (SLO) BK potassium channel. Consistent with this, slo mutant larvae exhibit similar alterations in synapse morphology, active zone size and neurotransmission, and simultaneous loss of dysc and slo does not enhance these phenotypes, suggesting that dysc and slo act in a common genetic pathway to modulate synaptic development and output. Our data expand our understanding of the neuronal functions of DYSC and uncover non-canonical roles for the SLO potassium channel at Drosophila synapses.

Original languageEnglish (US)
Pages (from-to)4548-4557
Number of pages10
JournalDevelopment
Volume141
Issue number23
DOIs
StatePublished - Dec 1 2014

Fingerprint

Drosophila Proteins
Synaptic Transmission
Drosophila
Potassium Channels
Synapses
Usher Syndromes
Large-Conductance Calcium-Activated Potassium Channels
PDZ Domains
Proteins
Neuronal Plasticity
Neuromuscular Junction
Blindness
Ion Channels
Larva
Neurotransmitter Agents
Catalytic Domain
Phenotype

Keywords

  • Active zone
  • BK channel
  • Drosophila
  • Neuromuscular junction
  • PDZ domain
  • Scaffold protein

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Jepson, J. E. C., Shahidullah, M., Liu, D., le Marchand, S. J., Liu, S., Wu, M., ... Koh, K. (2014). Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic. Development, 141(23), 4548-4557. https://doi.org/10.1242/dev.109538

Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic. / Jepson, James E C; Shahidullah, Mohammed; Liu, Die; le Marchand, Sylvain J.; Liu, Sha; Wu, Mark; Levitan, Irwin B.; Dalva, Matthew B.; Koh, Kyunghee.

In: Development, Vol. 141, No. 23, 01.12.2014, p. 4548-4557.

Research output: Contribution to journalArticle

Jepson, JEC, Shahidullah, M, Liu, D, le Marchand, SJ, Liu, S, Wu, M, Levitan, IB, Dalva, MB & Koh, K 2014, 'Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic', Development, vol. 141, no. 23, pp. 4548-4557. https://doi.org/10.1242/dev.109538
Jepson JEC, Shahidullah M, Liu D, le Marchand SJ, Liu S, Wu M et al. Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic. Development. 2014 Dec 1;141(23):4548-4557. https://doi.org/10.1242/dev.109538
Jepson, James E C ; Shahidullah, Mohammed ; Liu, Die ; le Marchand, Sylvain J. ; Liu, Sha ; Wu, Mark ; Levitan, Irwin B. ; Dalva, Matthew B. ; Koh, Kyunghee. / Regulation of synaptic development and function by the Drosophila PDZ protein Dyschronic. In: Development. 2014 ; Vol. 141, No. 23. pp. 4548-4557.
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