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Iyer, J., Wahlmark, C.J., Kuser-Ahnert, G.A., Kawasaki, F. (2013). Molecular mechanisms of COMPLEXIN fusion clamp function in synaptic exocytosis revealed in a new Drosophila mutant.  Mol. Cell. Neurosci. 56C(): 244--254.
FlyBase ID
FBrf0222891
Publication Type
Research paper
Abstract

The COMPLEXIN (CPX) proteins play a critical role in synaptic vesicle fusion and neurotransmitter release. Previous studies demonstrated that CPX functions in both activation of evoked neurotransmitter release and inhibition/clamping of spontaneous synaptic vesicle fusion. Here we report a new cpx mutant in Drosophila melanogaster, cpx(1257), revealing spatially defined and separable pools of CPX which make distinct contributions to the activation and clamping functions. In cpx(1257), lack of only the last C-terminal amino acid of CPX is predicted to disrupt prenylation and membrane targeting of CPX. Immunocytochemical analysis established localization of wild-type CPX to active zone (AZ) regions containing neurotransmitter release sites as well as broader presynaptic membrane compartments including synaptic vesicles. Parallel biochemical studies confirmed CPX membrane association and demonstrated robust binding interactions of CPX with all three SNAREs. This is in contrast to the cpx(1257) mutant, in which AZ localization of CPX persists but general membrane localization and, surprisingly, the bulk of CPX-SNARE protein interactions are abolished. Furthermore, electrophysiological analysis of neuromuscular synapses revealed interesting differences between cpx(1257) and a cpx null mutant. The cpx null exhibited a marked decrease in the EPSC amplitude, slowed EPSC rise and decay times and an increased mEPSC frequency with respect to wild-type. In contrast, cpx(1257) exhibited a wild-type EPSC with an increased mEPSC frequency and thus a selective failure to clamp spontaneous release. These results indicate that spatially distinct and separable interactions of CPX with presynaptic membranes and SNARE proteins mediate separable activation and clamping functions of CPX in neurotransmitter release.

PubMed ID
PubMed Central ID
PMC3791175 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Cell. Neurosci.
    Title
    Molecular and Cellular Neurosciences
    Publication Year
    1990-
    ISBN/ISSN
    1044-7431
    Data From Reference
    Aberrations (2)
    Alleles (6)
    Genes (7)
    Physical Interactions (3)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (4)