Frequenin/NCS-1 and the Ca2+-channel α1-subunit co-regulate synaptic transmission and nerve-terminal growth

  1. Dason, Jeffrey S. 1
  2. Romero-Pozuelo, Jesús 2
  3. Marin, Leo 1
  4. Iyengar, Balaji G. 1
  5. Klose, Markus K. 1
  6. Ferrús, Alberto 2
  7. Atwood, Harold L. 1
  1. 1 Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
  2. 2 Instituto Cajal, CSIC, Ave. Dr Arce 37, Madrid 28002, Spain
Revista:
Journal of Cell Science

ISSN: 1477-9137,  0021-9533

Año de publicación: 2009

Volumen: 122

Número: 22

Páginas: 4109-4121

Tipo: Artículo

DOI: 10.1242/JCS.055095 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Journal of Cell Science

Resumen

Drosophila Frequenin (Frq) and its mammalian and worm homologue, NCS-1, are Ca2+-binding proteins involved in neurotransmission. Using site-specific recombination in Drosophila, we created two deletions that removed the entire frq1 gene and part of the frq2 gene, resulting in no detectable Frq protein. Frq-null mutants were viable, but had defects in larval locomotion, deficient synaptic transmission, impaired Ca2+ entry and enhanced nerve-terminal growth. The impaired Ca2+ entry was sufficient to account for reduced neurotransmitter release. We hypothesized that Frq either modulates Ca2+ channels, or that it regulates the PI4Kpathway as described in other organisms. To determine whether Frq interacts with PI4K with consequent effects on Ca2+ channels, we first characterized a PI4K-null mutant and found that PI4K was dispensable for synaptic transmission and nerveterminal growth. Frq gain-of-function phenotypes remained present in a PI4K-null background. We conclude that the effects of Frq are not due to an interaction with PI4K. Using flies that were trans-heterozygous for a null frq allele and a null cacophony (encoding the 1-subunit of voltage-gated Ca2+ channels) allele, we show a synergistic effect between these proteins in neurotransmitter release. Gain-of-function Frq phenotypes were rescued by a hypomorphic cacophony mutation. Overall, Frq modulates Ca2+ entry through a functional interaction with the 1 voltage-gated Ca2+-channel subunit; this inter

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