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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M502191200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Activating the Astrocytes of the Dorsal Raphe Nucleus via Its Neural Circuits With the Medial Prefrontal Cortex Improves Depression in Mice.
Behav Neurol
January 2025
Laboratory of Neurobiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Astrocytes are the primary cell type in the central nervous system, responsible for maintaining the stability of the brain's internal environment and supporting neuronal functions. Researches have demonstrated the close relationship between astrocytes and the pathophysiology and etiology of major depressive disorder. However, the regulatory mechanisms of astrocytes during depression remain unclear.
View Article and Find Full Text PDFCamk2n1 deficiency reduces the NaCl cotransporter activity through the CUL3/KLHL3/WNK4 complex in the kidney.
Eur J Pharmacol
January 2025
Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Calcium/calmodulin dependent protein kinase II inhibitor 1 (Camk2n1) is closely associated with a peak logarithm of odds score in quantitative trait loci for systolic blood pressure. Increased Camk2n1 mRNA expression has been specifically observed in the kidneys of hypertension mouse models. However, the precise role of Camk2n1 in the kidney remains unclear.
View Article and Find Full Text PDFRole of PI3 Kinases in Cell Signaling and Soleus Muscle Atrophy During Three Days of Unloading.
Int J Mol Sci
January 2025
Myology Laboratory, Institute of Biomedical Problems (IBP), RAS, 123007 Moscow, Russia.
During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3Kγ), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes.
View Article and Find Full Text PDFChronic exposure to high altitudes causes pathophysiological cardiac changes that are characterized by cardiac dysfunction, cardiac hypertrophy, and decreased energy reserves. However, finding specific pharmacological interventions for these pathophysiological changes is challenging. In this study, we identified tetramethylpyrazine (TMP) as a promising drug candidate for cardiac dysfunction caused by simulated high-altitude exposure.
View Article and Find Full Text PDFCalcium calmodulin kinase IV deficiency in podocytes prevents the development of lupus nephritis.
Clin Immunol
January 2025
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States of America.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ involvement including the kidney. Calcium/calmodulin-dependent protein kinase IV (CaMK4) has been shown to conrol immune cell nad podocyte function. To address the effect of genetic podocyte-specific CaMK4 deficiency on systemic autoimmunity and kidney pathology in lupus-prone mice we generated B6.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!