RGD Reference Report - Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2.

General

Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2.
Authors:	Robison, AJ Bass, MA Jiao, Y MacMillan, LB Carmody, LC Bartlett, RK Colbran, RJ
Citation:	Robison AJ, etal., J Biol Chem. 2005 Oct 21;280(42):35329-36. Epub 2005 Aug 24.
RGD ID:	2314407
Pubmed:	PMID:16120608 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M502191200 (Journal Full-text)
Dendritic calcium/calmodulin-dependent protein kinase II (CaMKII) is dynamically targeted to the synapse. We show that CaMKIIalpha is associated with the CaMKII-binding proteins densin-180, the N-methyl-D-aspartate receptor NR2B subunit, and alpha-actinin in postsynaptic density-enriched rat brain fractions. Residues 819-894 within the C-terminal domain of alpha-actinin-2 constitute the minimal CaMKII-binding domain. Similar amounts of Thr286-autophosphorylated CaMKIIalpha holoenzyme [P-T286]CaMKII bind to alpha-actinin-2 as bind to NR2B (residues 1260-1339) or to densin-180 (residues 1247-1495) in glutathione-agarose cosedimentation assays, even though the CaMKII-binding domains share no amino acid sequence similarity. Like NR2B, alpha-actinin-2 binds to representative splice variants of each CaMKII gene (alpha, beta, gamma, and delta), whereas densin-180 binds selectively to CaMKIIalpha. In addition, C-terminal truncated CaMKIIalpha monomers can interact with NR2B and alpha-actinin-2, but not with densin-180. Soluble alpha-actinin-2 does not compete for [P-T286]CaMKII binding to immobilized densin-180 or NR2B. However, soluble densin-180, but not soluble NR2B, increases CaMKII binding to immobilized alpha-actinin-2 by approximately 10-fold in a PDZ domain-dependent manner. A His6-tagged NR2B fragment associates with GST-densin or GST-actinin but only in the presence of [P-T286]CaMKII. Similarly, His6-tagged densin-180 or alpha-actinin fragments associate with GST-NR2B in a [P-T286]CaMKII-dependent manner. In addition, GST-NR2B and His6-tagged alpha-actinin can bind simultaneously to monomeric CaMKII subunits. In combination, these data support a model in which [P-T286]CaMKIIalpha can simultaneously interact with multiple dendritic spine proteins, possibly stabilizing the synaptic localization of CaMKII and/or nucleating a multiprotein synaptic signaling complex.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
protein binding	enables	IPI	UniProtKB:P70587	2314407	PMID:16120608	IntAct
protein binding	enables	IPI	UniProtKB:P11798	2314407; 2314407	PMID:16120608	IntAct
protein binding	enables	IPI	UniProtKB:P11275	2314407	PMID:16120608	IntAct
protein kinase binding		IPI	Camk2a (Rattus norvegicus)	2314407		RGD

Objects Annotated

Genes (Rattus norvegicus)

Camk2a (calcium/calmodulin-dependent protein kinase II alpha)

Grin2b (glutamate ionotropic receptor NMDA type subunit 2B)

Lrrc7 (leucine rich repeat containing 7)

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Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2.