The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy

A. Ashleigh Long, Cecon T. Mahapatra, Elvin A. Woodruff, Jeff Rohrbough, Hung Tat Leung, Shikoh Shino, Lingling An, Rebecca W. Doerge, Mark M. Metzstein, William L. Pak, Kendal Broadie

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

A systematic Drosophila forward genetic screen for photoreceptor synaptic transmission mutants identified no-on-and-no-off transient C (nonC) based on loss of retinal synaptic responses to light stimulation. The cloned gene encodes phosphatidylinositol-3-kinase-like kinase (PIKK) Smg1, a regulatory kinase of the nonsense-mediated decay (NMD) pathway. The Smg proteins act in an mRNA quality control surveillance mechanism to selectively degrade transcripts containing premature stop codons, thereby preventing the translation of truncated proteins with dominant-negative or deleterious gain-of-function activities. At the neuromuscular junction (NMJ) synapse, an extended allelic series of Smg1 mutants show impaired structural architecture, with decreased terminal arbor size, branching and synaptic bouton number. Functionally, loss of Smg1 results in a ∼50% reduction in basal neurotransmission strength, as well as progressive transmission fatigue and greatly impaired synaptic vesicle recycling during high-frequency stimulation. Mutation of other NMD pathways genes (Upf2 and Smg6) similarly impairs neurotransmission and synaptic vesicle cycling. These findings suggest that the NMD pathway acts to regulate proper mRNA translation to safeguard synapse morphology and maintain the efficacy of synaptic function.

Original languageEnglish (US)
Pages (from-to)3303-3315
Number of pages13
JournalJournal of Cell Science
Volume123
Issue number19
DOIs
StatePublished - Oct 1 2010

Fingerprint

Synaptic Vesicles
Synaptic Transmission
Synapses
Nonsense Codon
Protein Biosynthesis
Phosphotransferases
Phosphatidylinositol 3-Kinase
Neuromuscular Junction
Presynaptic Terminals
Quality Control
Genes
Drosophila
Fatigue
Light
Messenger RNA
Proteins

Keywords

  • Drosophila
  • mRNA regulation
  • Neurotransmission
  • NMD pathway
  • Photoreceptor
  • Smg1
  • Synapse
  • Synaptic vesicle cycle

ASJC Scopus subject areas

  • Cell Biology

Cite this

Long, A. A., Mahapatra, C. T., Woodruff, E. A., Rohrbough, J., Leung, H. T., Shino, S., ... Broadie, K. (2010). The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy. Journal of Cell Science, 123(19), 3303-3315. https://doi.org/10.1242/jcs.069468

The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy. / Long, A. Ashleigh; Mahapatra, Cecon T.; Woodruff, Elvin A.; Rohrbough, Jeff; Leung, Hung Tat; Shino, Shikoh; An, Lingling; Doerge, Rebecca W.; Metzstein, Mark M.; Pak, William L.; Broadie, Kendal.

In: Journal of Cell Science, Vol. 123, No. 19, 01.10.2010, p. 3303-3315.

Research output: Contribution to journalArticle

Long, AA, Mahapatra, CT, Woodruff, EA, Rohrbough, J, Leung, HT, Shino, S, An, L, Doerge, RW, Metzstein, MM, Pak, WL & Broadie, K 2010, 'The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy', Journal of Cell Science, vol. 123, no. 19, pp. 3303-3315. https://doi.org/10.1242/jcs.069468
Long AA, Mahapatra CT, Woodruff EA, Rohrbough J, Leung HT, Shino S et al. The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy. Journal of Cell Science. 2010 Oct 1;123(19):3303-3315. https://doi.org/10.1242/jcs.069468
Long, A. Ashleigh ; Mahapatra, Cecon T. ; Woodruff, Elvin A. ; Rohrbough, Jeff ; Leung, Hung Tat ; Shino, Shikoh ; An, Lingling ; Doerge, Rebecca W. ; Metzstein, Mark M. ; Pak, William L. ; Broadie, Kendal. / The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy. In: Journal of Cell Science. 2010 ; Vol. 123, No. 19. pp. 3303-3315.
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