Neurogranin controls the spatiotemporal pattern of postsynaptic Ca2+/CaM signaling.
Biophys J
; 93(11): 3848-59, 2007 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-17704141
ABSTRACT
Neurogranin (Ng) is a postsynaptic IQ-motif containing protein that accelerates Ca(2+) dissociation from calmodulin (CaM), a key regulator of long-term potentiation and long-term depression in CA1 pyramidal neurons. The exact physiological role of Ng, however, remains controversial. Two genetic knockout studies of Ng showed opposite outcomes in terms of the induction of synaptic plasticity. To understand its function, we test the hypothesis that Ng could regulate the spatial range of action of Ca(2+)/CaM based on its ability to accelerate the dissociation of Ca(2+) from CaM. Using a mathematical model constructed on the known biochemistry of Ng, we calculate the cycle time that CaM molecules alternate between the fully Ca(2+) saturated state and the Ca(2+) unbound state. We then use these results and include diffusion of CaM to illustrate the impact that Ng has on modulating the spatial profile of Ca(2+)-saturated CaM within a model spine compartment. Finally, the first-passage time of CaM to transition from the Ca(2+)-free state to the Ca(2+)-saturated state was calculated with or without Ng present. These analyses suggest that Ng regulates the encounter rate between Ca(2+) saturated CaM and its downstream targets during postsynaptic Ca(2+) transients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
/
Calmodulina
/
Células Piramidais
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Potenciais Pós-Sinápticos Excitadores
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Sinalização do Cálcio
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Neurogranina
/
Modelos Neurológicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article