Abstract

The overall objective of this project is to gain deeper understanding of fiber type-specific gene expression skeletal muscle and of calcium signalling in muscle and neurons. Activity dependent gene expression will be studied in skeletal muscle and role of cytosolic [Ca/2+] in such """"""""excitation-transcription"""""""" (ET) coupling will be determined. Understand of the mechanisms of ET coupling is of central importance for maintenance of muscle tone and function in health, inactivity and after traumatic nerve section or during neuromuscular disease. The subcellular details of calcium signaling will be explored in isolated neurons to explain important local effects of [Ca/2+] relevant to wide range of neuronal functions. The contributions of Ca/2+ transport systems and Ca/2+ binding proteins to the decline of muscle [Ca/2+] after Ca/2+ release, which is crucial to the relaxation of normal and diseased muscle, will be determined for both fast-and slow-twitch muscle. Chronic electrical stimulation will be used to study plasticity of gene expression in individual enzymatically isolated adult mouse skeletal muscle fibers in culture. The localization and functional properties of the calcium uptake, storage, and release organelles in neurons will be determined by high spatio-temporal resolution confocal microscopy of individual sympathetic ganglion neurons. Protein isoform composition will be determined in the same individual muscle fibers from which [Ca/2+] transients were recorded to define the molecular basis for the diversity of calcium removal mechanisms in fibers of the same and different types. These studies will provide a better understanding of the cellular and molecular mechanisms underlying fiber type conversion in skeletal muscle, the control of a variety of calcium dependent processes in both muscle and neurons, and relaxation of skeletal muscle fibers. They will provide deeper insight into calcium regulation and its adaptability in muscle and neurons under a variety of physiological states as well as during disuse, aging and under possible pathological conditions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS033578-08
Application #
6476087
Study Section
Special Emphasis Panel (ZRG1-MDCN-4 (01))
Program Officer
Nichols, Paul L
Project Start
1994-05-01
Project End
2003-06-30
Budget Start
2001-12-01
Budget End
2003-06-30
Support Year
8
Fiscal Year
2002
Total Cost
$253,016
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Biochemistry
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Liu, Yewei; Contreras, Minerva; Shen, Tiansheng et al. (2009) Alpha-adrenergic signalling activates protein kinase D and causes nuclear efflux of the transcriptional repressor HDAC5 in cultured adult mouse soleus skeletal muscle fibres. J Physiol 587:1101-15
Mu, Xiaodong; Brown, Lisa D; Liu, Yewei et al. (2007) Roles of the calcineurin and CaMK signaling pathways in fast-to-slow fiber type transformation of cultured adult mouse skeletal muscle fibers. Physiol Genomics 30:300-12
Shen, Tiansheng; Cseresnyes, Zoltan; Liu, Yewei et al. (2007) Regulation of the nuclear export of the transcription factor NFATc1 by protein kinases after slow fibre type electrical stimulation of adult mouse skeletal muscle fibres. J Physiol 579:535-51
Shen, Tiansheng; Liu, Yewei; Randall, William R et al. (2006) 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. J Muscle Res Cell Motil 27:405-11
Shen, Tiansheng; Liu, Yewei; Cseresnyes, Zoltan et al. (2006) Activity- and calcineurin-independent nuclear shuttling of NFATc1, but not NFATc3, in adult skeletal muscle fibers. Mol Biol Cell 17:1570-82
Liu, Yewei; Randall, William R; Schneider, Martin F (2005) Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle. J Cell Biol 168:887-97
Liu, Yewei; Shen, Tiansheng; Randall, William R et al. (2005) Signaling pathways in activity-dependent fiber type plasticity in adult skeletal muscle. J Muscle Res Cell Motil 26:13-21
Cseresnyes, Zoltan; Schneider, Martin F (2004) Peripheral hot spots for local Ca2+ release after single action potentials in sympathetic ganglion neurons. Biophys J 86:163-81
Brown, L D; Schneider, M F (2002) Delayed dedifferentiation and retention of properties in dissociated adult skeletal muscle fibers in vitro. In Vitro Cell Dev Biol Anim 38:411-22
Liu, Y; Cseresnyes, Z; Randall, W R et al. (2001) Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. J Cell Biol 155:27-39

Showing the most recent 10 out of 20 publications