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Event: 1243

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Altered, Ca2+-calmodulin activated signal transduction

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
binding	calcium ion	abnormal
signaling	calmodulin	abnormal
calmodulin binding	calcium ion	abnormal

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status
nAChR activation - colony loss 6	KeyEvent	Brendan Ferreri-Hanberry (send email)	Open for comment. Do not cite
nAChR activation - colony loss 7	KeyEvent	Arthur Author (send email)	Open for comment. Do not cite
nAChR activation - colony death 1	KeyEvent	Agnes Aggy (send email)	Open for comment. Do not cite
nAChR activation - colony loss 5	KeyEvent	Cataia Ives (send email)	Open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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 channels • 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

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

References

List of the literature that was cited for this KE description. More help

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.