Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-7
pubmed:dateCreated
2006-8-30
pubmed:abstractText
Skeletal muscle fibers exhibit plasticity of their physiological and biochemical properties in response to the firing pattern from the innervating motor neuron. In particular, the gene expression pattern generally characteristic of a slow twitch fiber can be induced in a fast twitch fiber by chronic slow fiber type electrical stimulation. We have studied the nucleo-cytoplasmic distribution of two transcriptional regulators of slow fiber type genes, HDAC4 and NFATc1, both in response to slow fiber type stimulation and in resting conditions using cultured fast twitch skeletal muscle fibers. HDAC4 is present in both cytoplasm and nuclei of resting fibers, and moves out of the nuclei in response to slow fiber type stimulation. The stimulation-dependent nuclear efflux of HDAC4 requires activation of nuclear CaMKII, which phosphorylates nuclear HDAC4 and thus allows its exit of the nucleus. In unstimulated resting fibers, a balance of nuclear efflux and influx of HDAC4 establishes the resting level of nuclear HDAC4. However, the nuclear efflux of HDAC4 in resting fibers does not involve CaMKII. Slow fiber type stimulation also causes NFATc1 translocation from the cytoplasm into muscle fiber nuclei following dephosphorylation by calcineurin (CaN) activated by the elevated cytosolic Ca2+ accompanying fiber stimulation. In resting fibers, NFATc1 exhibits balanced shuttling between cytoplasm and nucleus, but during this shuttling NFATc1 influx does not require CaN and NFATc1 efflux does not require the kinases involved in removing nuclear NFATc1 following prior activity. Thus different enzymes are responsible for HDAC4 nuclear efflux in resting and active fibers, and different pathways mediate NFATc1 nuclear influx and efflux in resting and active fibers. Such dual mechanisms for resting shuttling and active movements provide the potential for the resting level and the rate of translocation during fiber stimulation to be controlled independently for both of the transcriptional regulators HDAC4 and NFATc1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0142-4319
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
405-11
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Parallel mechanisms for resting nucleo-cytoplasmic shuttling and activity dependent translocation provide dual control of transcriptional regulators HDAC and NFAT in skeletal muscle fiber type plasticity.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201-1503, USA.
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural