Nuclear targeting of the CaMKII anchoring protein alphaKAP is regulated by alternative splicing and protein kinases

Brain Research
Heather O'LearyK Ulrich Bayer

Abstract

alphaKAP is an anchoring protein for the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and is encoded within the same gene as the CaMKIIalpha isoform. alphaKAP co-assembles with CaMKII and targets such heteromers to the membrane of the sarcoplasmic reticulum, where CaMKII can regulate Ca(2+) homeostasis. CaMKII has also nuclear functions in skeletal muscle, however, the nuclear targeting mechanism has been elusive. We show here that developmentally regulated splicing of exon Ealpha(B) generates a functional nuclear localization signal (NLS) in alphaKAP(B), the dominant alphaKAP variant in mature muscle. The alphaKAP(A) variant lacks the NLS and dominates in developing muscle before and around birth. Both alphaKAP variants localize to membranes, but a small fraction of alphaKAP(B) is additionally found in the nucleus. Indeed, alpha-karyopherins that mediate nuclear import bound to alphaKAP(B) but not alphaKAP(A) in vitro. When the N-terminal membrane anchor of alphaKAP was deleted, localization of alphaKAP(B) but not alphaKAP(A) became predominantly nuclear. Co-expression of constitutively active CaMKI and IV, which do not bind to alphaKAP, interfered with nuclear localization of alphaKAP(B). CaMKIIalpha was found essen...Continue Reading

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Citations

Dec 15, 2012·Journal of Cellular Biochemistry·Zaira AversaPer-Olof Hasselgren
Jun 7, 2014·Frontiers in Aging Neuroscience·Rüdiger RudolfMichael R Deschenes
Aug 23, 2012·Gene·Olga KelemenStefan Stamm
Jun 17, 2016·American Journal of Physiology. Cell Physiology·Fanny ToussaintJonathan Ledoux

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