Neurogranin (Ng) is a 78-amino-acid-long protein concentrated at dendritic spines of forebrain neurons that is involved in synaptic plasticity through the regulation of CaM (calmodulin)-mediated signalling. Ng features a central IQ motif that mediates binding to CaM and is phosphorylated by PKC (protein kinase C). We have analysed the subcellular distribution of Ng and found that it associates to cellular membranes in rat brain. In vitro binding assays revealed that Ng selectively binds to PA (phosphatidic acid) and that this interaction is prevented by CaM and PKC phosphorylation. Using the peptide Ng-(29–47) and a mutant with an internal deletion (Ng-IQless), we have shown that Ng binding to PA and to cellular membranes is mediated by its IQ motif. Ng expressed in NIH-3T3 cells accumulates at peripheral regions of the plasma membrane and localizes at intracellular vesicles that can be clearly visualized following saponin permeabilization. This distribution was affected by PLD (phospholipase D) and PIP5K (phosphatidylinositol 4-phosphate 5-kinase) overexpression. Based on these results, we propose that Ng binding to PA may be involved in Ng accumulation at dendritic spines and that Ng could modulate PA signalling in the postsynaptic environment.
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Research Article|
April 26 2007
Neurogranin binds to phosphatidic acid and associates to cellular membranes
Irene Domínguez-González;
Irene Domínguez-González
1Departamento de Biología Molecular and Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), E-28049, Madrid, Spain
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Silvia N. Vázquez-Cuesta;
Silvia N. Vázquez-Cuesta
1Departamento de Biología Molecular and Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), E-28049, Madrid, Spain
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Alicia Algaba;
Alicia Algaba
1Departamento de Biología Molecular and Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), E-28049, Madrid, Spain
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F. Javier Díez-Guerra
F. Javier Díez-Guerra
1
1Departamento de Biología Molecular and Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), E-28049, Madrid, Spain
1To whom correspondence should be addressed (email fjdiez@cbm.uam.es).
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Publisher: Portland Press Ltd
Received:
September 28 2006
Revision Received:
February 08 2007
Accepted:
February 12 2007
Accepted Manuscript online:
February 12 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2007 Biochemical Society
2007
Biochem J (2007) 404 (1): 31–43.
Article history
Received:
September 28 2006
Revision Received:
February 08 2007
Accepted:
February 12 2007
Accepted Manuscript online:
February 12 2007
Citation
Irene Domínguez-González, Silvia N. Vázquez-Cuesta, Alicia Algaba, F. Javier Díez-Guerra; Neurogranin binds to phosphatidic acid and associates to cellular membranes. Biochem J 15 May 2007; 404 (1): 31–43. doi: https://doi.org/10.1042/BJ20061483
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