94 research outputs found
D.: Multilevel Societies in Primates and Other Mammals: Introduction to the Special Issue
No full text# The Author(s) 2012. This article is published with open access at Springerlink.co
TB36: Economic Analysis of Camping-oriented Recreation Firms: Part 1--Simulation of a Recreational Firm: Flow Chart and Computer Program
No full textThis computer program simulates the economic activities associated with the establishment and operation of a camping-oriented recreation firm and is designed for purposes of business analysis and decision making. The simulation model was developed for and tested by the author on the IBM 360 model 40 do-system computer at the University of Maine\u27s computing center.https://digitalcommons.library.umaine.edu/aes_techbulletin/1153/thumbnail.jp
Ca2+/Calmodulin-dependent Protein Kinase II Anchoring to L-type Ca2+ Channels by the Beta Subunits Enhances Regulatory Phosphorylation at Thr498
No full textCalcium/calmodulin-dependent kinase II (CaMKII) facilitates L-type calcium channel (LTCC) activity physiologically, but may exacerbate LTCC-dependent pathophysiology. We previously showed that CaMKII forms stable complexes with voltage-gated calcium channel (VGCC) β1b or β2a subunits, but not with the β3 or β4 subunits (Grueter et al. 2008). CaMKII-dependent facilitation of CaV1.2 LTCCs requires Thr498 phosphorylation in the β2a subunit (Grueter et al. 2006), but the relationship of this modulation to CaMKII interactions with LTCC subunits is unknown. Here we show that CaMKII co-immunoprecipitates with forebrain LTCCs that contain CaV1.2α1 and β1 or β2 subunits, but is not detected in LTCC complexes containing β4 subunits. CaMKIIα can be specifically tethered to the I/II linker of CaV1.2 α1 subunits in vitro by the β1b or β2a subunits. Efficient targeting of CaMKIIα to the full-length CaV1.2α1 subunit in transfected HEK293 cells requires CaMKII binding to the β2a subunit. Moreover, disruption of CaMKII binding substantially reduced phosphorylation of β2a at Thr498 within the LTCC complex, without altering overall phosphorylation of CaV1.2α1 and β subunits. These findings demonstrate a biochemical mechanism underlying LTCC facilitation by CaMKII
Corrigendum: A Severe Lack of Evidence Limits Effective Conservation of the World's Primates
No full textIn the originally published version of this article, the author's name, Kathy Slater, was incorrectly spelt in the author list and within the “Author Biographical” section. This has now been corrected online.Additional co-authors: Fabiano R de MELO, P Fan, Cyril C Grueter, Diana C Guzmán-Caro, Eckhard W Heymann, Ilka Herbinger, Minh D Hoang, Robert H Horwich, Tatyana Humle, Rachel A Ikemeh, Inaoyom S Imong, Leandro Jerusalinsky, Steig E Johnson, Peter M Kappeler, Maria Cecília M Kierulff, Inza Koné, Rebecca Kormos, Khac Q LE, Baoguo Li, Andrew J Marshall, Erik Meijaard, Russel A Mittermeier, Yasuyuki Muroyama, Eleonora Neugebauer, Lisa Orth, Erwin Palacios, Sarah K Papworth, Andrew J Plumptre, Ben M Rawson, Johannes Refisch, Jonah Ratsimbazafy, Christian Roos, Joanna M Setchell, Rebecca K Smith, Tene Sop, Christoph Schwitzer, Kathy Slater, Shirley C Strum, William J Sutherland, Maurício Talebi, Janette Wallis, Serge Wich, Roman M Wittig, Hjalmar S Küh
Ca2+/calmodulin-dependent protein kinase II regulates cardiac l-type Ca2+ channels via the beta subunit
No full textHeart disease is the number one cause of death in the United States. There are many forms of heart disease including heart failure and arrhythmias. One underlying theme in heart disease and many other diseases is disrupted Ca2+ homeostasis. Calcium is a charge carrier and universal mediator of diverse cellular processes. In cardiac myocytes, these processes include excitation-contraction coupling, gene transcription and apoptosis.
Ca2+ enters cardiac myocytes through L-type Ca2+ channels (LTCC) where it activates signaling molecules such as the multifunctional Ca2+/calmodulin dependent protein kinase II (CaMKII). CaMKII is one of many specialized proteins poised to respond to Ca2+ signaling in cardiac myocytes. Accumulating evidence links cardiac CaMKII activity to normal physiological regulation of several heart functions and to multiple pathological conditions.
CaMKII is associated with cardiac LTCC complexes and increases channel open probability (PO) to dynamically increase Ca2+ current (ICa) and augment cellular Ca2+ signaling by a process called facilitation. I found that activated CaMKII binds to the LTCC b2a subunit close to a preferred CaMKII phosphorylation site, Thr498 and colocalizes with b2a in cardiomyocytes. Mutation of Thr498 to Ala (T498A) in b2a prevents CaMKII-mediated increases in the PO of recombinant LTCCs. Moreover, expression of b2a (T498A) in adult cardiomyocytes ablates CaMKII-mediated ICa facilitation, demonstrating that phosphorylation of b2a at Thr498 modulates native Ca2+ channels.
In addition, I showed that binding requires CaMKII activation but phosphorylation at Thr498 inhibits binding. The b2a subunit also modulates CaMKII activity and enhances CaMKII autophosphorylation at a site other than Thr287 or Thr305/306. Analysis of the primary sequences of the four b isoforms reveal that the CaMKII binding/regulatory site is conserved in b1b but not in b3 nor b4 and CaMKII was shown to interact with b1b in a similar manner as b2a.
Taken together these findings reveal a novel molecular mechanism for dynamic targeting of CaMKII to LTCCs and facilitating ICa that may modulate Ca2+ entry in diverse cell types co-expressing CaMKII and the b2a subunit. Future work based on these findings may identify a potential pharmacological target for the treatment of heart disease or other pathological conditions involving disrupted Ca2+ homeostasis
Differential Regulated Interactions of Calcium/Calmodulin-Dependent Protein Kinase II with Isoforms of Voltage-Gated Calcium Channel β Subunits<sup>†</sup>
No full textCa2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylates the β2a subunit of
voltage-gated Ca2+ channels at Thr498 to facilitate cardiac L-type Ca2+ channels. CaMKII colocalizes
with β2a in cardiomyocytes and also binds to a domain in β2a that contains Thr498 and exhibits an amino
acid sequence similarity to the CaMKII autoinhibitory domain and to a CaMKII binding domain in the
NMDA receptor NR2B subunit (Grueter, C. E. et al. (2006) Mol. Cell 23, 641). Here, we explore the
selectivity of the actions of CaMKII among Ca2+ channel β subunit isoforms. CaMKII phosphorylates
the β1b, β2a, β3, and β4 isoforms with similar initial rates and final stoichiometries of 6−12 mol of phosphate
per mol of protein. However, activated/autophosphorylated CaMKII binds to β1b and β2a with a similar
apparent affinity but does not bind to β3 or β4. Prephosphorylation of β1b and β2a by CaMKII substantially
reduces the binding of autophosphorylated CaMKII. Residues surrounding Thr498 in β2a are highly
conserved in β1b but are different in β3 and β4. Site-directed mutagenesis of this domain in β2a showed
that Thr498 phosphorylation promotes dissociation of CaMKII-β2a complexes in vitro and reduces
interactions of CaMKII with β2a in cells. Mutagenesis of Leu493 to Ala substantially reduces CaMKII
binding in vitro and in intact cells but does not interfere with β2a phosphorylation at Thr498. In combination,
these data show that phosphorylation dynamically regulates the interactions of specific isoforms of the
Ca2+ channel β subunits with CaMKII
Creep Crack Growth in austenitic steels ? applicability of fracture mechanics parameters
No full textCa2+/calmodulin-dependent protein kinase II regulates cardiac l-type Ca2+ channels via the beta subunit
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