Neurogranin targets calmodulin and lowers the threshold for the induction of long-term potentiation. PLoS One 2012;7(7):e41275
Date
08/01/2012Pubmed ID
22848456Pubmed Central ID
PMC3405117DOI
10.1371/journal.pone.0041275Scopus ID
2-s2.0-84864327438 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Calcium entry and the subsequent activation of CaMKII trigger synaptic plasticity in many brain regions. The induction of long-term potentiation (LTP) in the CA1 region of the hippocampus requires a relatively high amount of calcium-calmodulin. This requirement is usually explained, based on in vitro and theoretical studies, by the low affinity of CaMKII for calmodulin. An untested hypothesis, however, is that calmodulin is not randomly distributed within the spine and its targeting within the spine regulates LTP. We have previously shown that overexpression of neurogranin enhances synaptic strength in a calmodulin-dependent manner. Here, using post-embedding immunogold labeling, we show that calmodulin is not randomly distributed, but spatially organized in the spine. Moreover, neurogranin regulates calmodulin distribution such that its overexpression concentrates calmodulin closer to the plasma membrane, where a high level of CaMKII immunogold labeling is also found. Interestingly, the targeting of calmodulin by neurogranin results in lowering the threshold for LTP induction. These findings highlight the significance of calmodulin targeting within the spine in synaptic plasticity.
Author List
Zhong L, Gerges NZAuthor
Nashaat Gerges PhD Chair, Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calmodulin
Cell Membrane
Hippocampus
Long-Term Potentiation
Neurogranin
Rats
Rats, Sprague-Dawley
Spine
