CaMKIIbeta Binding to Stable F-actin in Vivo Regulates F-actin Filament Stability

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Oct 9

PMID 18840684

Citations 56

Authors

Yu-Chih Lin

Lori Redmond

Affiliations

Soon will be listed here.

Abstract

Ca2(+)/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase that is best known for its role in synaptic plasticity and memory. Multiple roles of CaMKII have been identified in the hippocampus, yet its role in developing neurons is less well understood. We show here that endogenous CaMKIIbeta, but not CaMKIIalpha, localized to prominent F-actin-rich structures at the soma in embryonic cortical neurons. Fluorescence recovery after photobleaching analyses of GFP-CaMKIIbeta binding interactions with F-actin in this CaMKIIalpha-free system indicated CaMKIIbeta binding depended upon a putative F-actin binding domain in the variable region of CaMKIIbeta. Furthermore, CaMKIIalpha decreased CaMKIIbeta binding to F-actin. We examined the interaction of CaMKIIbeta with stable and dynamic actin and show that CaMKIIbeta binding to F-actin was dramatically prolonged when F-actin was stabilized. CaMKIIbeta binding to stable F-actin was disrupted when it was bound by Ca2(+)/calmodulin or when it was highly phosphorylated, but not by kinase inactivity. Whereas CaMKIIbeta over-expression increased the prevalence of the F-actin-rich structures, disruption of CaMKIIbeta binding to F-actin reduced them. Taken together, these data suggest that CaMKIIbeta binding to stable F-actin is important for the in vivo maintenance of polymerized F-actin.

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References

Thiagarajan T, Piedras-Renteria E, Tsien R . alpha- and betaCaMKII. Inverse regulation by neuronal activity and opposing effects on synaptic strength. Neuron. 2002; 36(6):1103-14. DOI: 10.1016/s0896-6273(02)01049-8. View

Cho M, Cao X, Wang D, Tsien J . Dentate gyrus-specific manipulation of beta-Ca2+/calmodulin-dependent kinase II disrupts memory consolidation. Proc Natl Acad Sci U S A. 2007; 104(41):16317-22. PMC: 2042204. DOI: 10.1073/pnas.0703344104. View

Colbran R . Targeting of calcium/calmodulin-dependent protein kinase II. Biochem J. 2003; 378(Pt 1):1-16. PMC: 1223945. DOI: 10.1042/BJ20031547. View

Okamoto K, Nagai T, Miyawaki A, Hayashi Y . Rapid and persistent modulation of actin dynamics regulates postsynaptic reorganization underlying bidirectional plasticity. Nat Neurosci. 2004; 7(10):1104-12. DOI: 10.1038/nn1311. View

Schliwa M . Action of cytochalasin D on cytoskeletal networks. J Cell Biol. 1982; 92(1):79-91. PMC: 2112008. DOI: 10.1083/jcb.92.1.79. View

Miller S, Kennedy M . Distinct forebrain and cerebellar isozymes of type II Ca2+/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction. J Biol Chem. 1985; 260(15):9039-46. View

Rostas J, Seccombe M, Weinberger R . Two developmentally regulated isoenzymes of calmodulin-stimulated protein kinase II in rat forebrain. J Neurochem. 1988; 50(3):945-53. DOI: 10.1111/j.1471-4159.1988.tb03003.x. View

Karls U, Muller U, Gilbert D, Copeland N, Jenkins N, Harbers K . Structure, expression, and chromosome location of the gene for the beta subunit of brain-specific Ca2+/calmodulin-dependent protein kinase II identified by transgene integration in an embryonic lethal mouse mutant. Mol Cell Biol. 1992; 12(8):3644-52. PMC: 364631. DOI: 10.1128/mcb.12.8.3644-3652.1992. View

Meador W, Means A, Quiocho F . Modulation of calmodulin plasticity in molecular recognition on the basis of x-ray structures. Science. 1993; 262(5140):1718-21. DOI: 10.1126/science.8259515. View

10.

Hanson P, Meyer T, Stryer L, Schulman H . Dual role of calmodulin in autophosphorylation of multifunctional CaM kinase may underlie decoding of calcium signals. Neuron. 1994; 12(5):943-56. DOI: 10.1016/0896-6273(94)90306-9. View

11.

Bubb M, Senderowicz A, Sausville E, Duncan K, Korn E . Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. J Biol Chem. 1994; 269(21):14869-71. View

12.

Mukherji S, Brickey D, Soderling T . Mutational analysis of secondary structure in the autoinhibitory and autophosphorylation domains of calmodulin kinase II. J Biol Chem. 1994; 269(32):20733-8. View

13.

Shen K, Teruel M, Subramanian K, Meyer T . CaMKIIbeta functions as an F-actin targeting module that localizes CaMKIIalpha/beta heterooligomers to dendritic spines. Neuron. 1998; 21(3):593-606. DOI: 10.1016/s0896-6273(00)80569-3. View

14.

Rich R, Schulman H . Substrate-directed function of calmodulin in autophosphorylation of Ca2+/calmodulin-dependent protein kinase II. J Biol Chem. 1998; 273(43):28424-9. DOI: 10.1074/jbc.273.43.28424. View

15.

Shen K, Meyer T . Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation. Science. 1999; 284(5411):162-6. DOI: 10.1126/science.284.5411.162. View

16.

Bayer K, Lohler J, Schulman H, Harbers K . Developmental expression of the CaM kinase II isoforms: ubiquitous gamma- and delta-CaM kinase II are the early isoforms and most abundant in the developing nervous system. Brain Res Mol Brain Res. 1999; 70(1):147-54. DOI: 10.1016/s0169-328x(99)00131-x. View

17.

Brocke L, Chiang L, Wagner P, Schulman H . Functional implications of the subunit composition of neuronal CaM kinase II. J Biol Chem. 1999; 274(32):22713-22. DOI: 10.1074/jbc.274.32.22713. View

18.

Hudmon A, Lebel E, Roy H, Sik A, Schulman H, Waxham M . A mechanism for Ca2+/calmodulin-dependent protein kinase II clustering at synaptic and nonsynaptic sites based on self-association. J Neurosci. 2005; 25(30):6971-83. PMC: 6724830. DOI: 10.1523/JNEUROSCI.4698-04.2005. View

19.

Shifman J, Choi M, Mihalas S, Mayo S, Kennedy M . Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by calmodulin with two bound calciums. Proc Natl Acad Sci U S A. 2006; 103(38):13968-73. PMC: 1599897. DOI: 10.1073/pnas.0606433103. View

20.

Hudmon A, Kim S, Kolb S, STOOPS J, Waxham M . Light scattering and transmission electron microscopy studies reveal a mechanism for calcium/calmodulin-dependent protein kinase II self-association. J Neurochem. 2001; 76(5):1364-75. DOI: 10.1046/j.1471-4159.2001.00119.x. View