Key Event Title
|Level of Biological Organization|
Key Event Components
|calmodulin binding||calcium ion||abnormal|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|nAChR activation - colony loss 6||KeyEvent|
|nAChR activation - colony loss 7||KeyEvent|
|nAChR activation - colony death 1||KeyEvent|
|nAChR activation - colony loss 5||KeyEvent|
Key Event Description
Text from LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:
"Some neuronal nAChR subunit combinations are highly permeable
to Ca2+, which acts as a messenger relaying extracellular information
to intracellular regions and to the nucleus (Uteshev, 2012). Upon influx
of Ca2+ into neurons via nAChR, Ca2+ binds to calmodulin (CaM). This
complex either activates adenylyl cyclase (AC) to catalyze the conversion
of ATP to 3′5′-adenosine monophosphate (cAMP),which then activates
PKA, or interacts with Ca2+-CaM kinase II (CaMKII) (e.g.,
Dajas-Bailador andWonnacott, 2004; Sweatt, 2001). Regardless of signaling
through PKA or CaMKII, both kinases activate the phosphorylation
cascade via extracellular signal-related protein kinase/mitogenactivated
protein kinase (ERK/MAPK), stimulating transcription of
cAMP response element (CRE) binding protein (CREB) mediated
genes (Impey et al., 1999). In neurons, these signaling cascades lead to
the production of proteins that direct synaptic plasticity (i.e., changes
in synaptic strength in response to signaling activity),which is essential
to learning and memory."
How It Is Measured or Detected
Text from Table 2 in LaLone et al. (2017) Weight of evidence evaluation of a network of adverse outcome pathways linking activaiton of the nicotinic acetylcholine receptor in honey bees to colony death. Science of the Total Environment 584-585, 751-775:
"• Fluorescent Ca2+ imaging in cells expressing nAChR for evaluation of Ca2+ levels entering individual nAChR-mediated ion
• Western blotting and kinase assays can be used to evaluate ERK1/2 phosphorylation and activity
• Activation of CREB/CRE transcription
• Pharmacological inhibition of pathway"
Domain of Applicability
LaLone, C.A., Villeneuve, D.L., Wu-Smart, J., Milsk, R.Y., Sappington, K., Garber, K.V., Housenger, J. and Ankley, G.T., 2017. Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death. STOTEN. 584-585, 751-775.
Uteshev, V.V., 2012. alpha7 nicotinic ACh receptors as a ligand-gated source of Ca(2+)
ions: the search for a Ca(2+) optimum. Adv. Exp. Med. Biol. 740, 603–638.
Dajas-Bailador, F., Wonnacott, S., 2004. Nicotinic acetylcholine receptors and the regulation
of neuronal signalling. Trends Pharmacol. Sci. 25 (6), 317–324.
Sweatt, J.D., 2001. The neuronalmap kinase cascade: a biochemical signal integration system
subserving synaptic plasticity and memory. J. Neurochem. 76, 1–10.
Impey, S., Obrietan, K., Storm, D.R., 1999. Making new connections: role of ERK/MAP kinase
signaling in neuronal plasticity. Neuron 23, 11–14.