Dr. Shakiryanova’s interests are focused on signaling mechanisms that regulate neuropeptide release and induce dense-core vesicles mobilization. Because neuropeptides control pain, appetite, mood, and sleep, understanding basic mechanisms underlying neuropeptide release could lead to clinical applications.

The vesicle motion, release and signal transduction in nerve terminals are detected optically by in vivo imaging of fluorescent protein constructs in transgenic Drosophila melanogaster larvae. Specifically, voltage-gated Ca²⁺ channels, Ca²⁺-induced Ca²⁺ release channels and Ca²⁺/calmodulin-activated kinase II are studied because they are required for sustained mobilization of peptidergic vesicles and post-tetanic potentiation of neuropeptide secretion.

Model of CamKII activation and translocation in the nerve terminal.

Global Ca2+ from Cav channels, IP3 receptors and ryanodine receptors combine to activate

presynaptic CamKII (red arrows). Then CamKII dodecamers cluster near Bruchpilot-containing

active zones (black arrows), where Ca2+ microdomains from Cav channels and endoplasmic

reticulum resident IP3 receptors are integrated.

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Important Publications

Shakiryanova D, GM Zettel, T Gu, RS Hewes and ES Levitan.  Synaptic neuropeptide release induced by octopamine wthout Ca2+ entry into the nerve terminal.  Proc Natl Acad Sci USA 108:4477-4481, 2011.

Shakiryanova D, T Morimoto, C Zhou, AK Chouhan, SJ Sigrist, A Nose, GT Macleod, DL Deitcher and ES Levitan.  Differential control of presynaptic (CaMKII) activation and translocation to active zones.  Journal of Neuroscience, in press, 2011.

Shakiryanova D and ES Levitan.  Prolonged presynaptic posttetanic cyclic GMP signaling in Drosophila motoneurons.  Proc Natl Acad SCI USA 105:13610-13613, 2008.

Shakiryanova D, MK Klose, Y Zhou, T Gu, DL Deitcher, HL Atwood, RS Hewes and ES Levitan. Vesicle mobilization and post-tetanic potentiation of neuropeptide release require ryanodine receptors and calmodulin kinase II. Journal of Neuroscience 27(29):7799-7806, 2007.

Shakiryanova D, A Tully and ES Levitan ES. Activity-dependent synaptic capture of transiting peptidergic vesicles.  Nature Neuroscience 9(7):896-900, 2006.

Shakiryanova D, A Tully, R Hewes, D Deitcher and ES Levitan . Activity-dependent liberation of synaptic neuropeptide vesicles. Nature Neuroscience 8(2): 173-178, 2005.