Biochemistry; Biophysics; Cell Biology; Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Molecular Virology: Virology laboratories
Mechanisms of membrane dynamics in relation to nuclear envelopathies and viral infection
Nuclear envelopathies are a diverse group of congenital diseases that are caused by mutations affecting proteins in the nuclear envelope or lamina. We hypothesize that envelopathy-associated alleles act at least in part through a gain of function mechanism that leads to a poisoning of nuclear membrane dynamics. Our goal is to unravel the cellular mechanisms that regulate protein homeostasis in the nuclear periphery, and to elucidate the role that these pathways play in muscular dystrophies, premature aging and related envelopathies. We exploit viral proteins known to manipulate the nuclear envelope as a novel approach to identify cellular factors involved in protein turnover and non-canonical nuclear transport via vesicular intermediates.
Specialized Terms: DYT1 Dystonia, Membrane dynamics; Torsin ATPases; Alternative nuclear transport (nuclear egress); Protein quality control; viral pathogenesis
- Torsin ATPases: structural insights and functional perspectives. Current Opinion in Cell Biology 40:1-7. Laudermilch, E, Schlieker, C. Current Opinion in Cell Biology (2016); 40:1-7.
- Torsins: not your typical AAA+ ATPases. Rose AE, Brown RS, Schlieker C. Crit Rev Biochem Mol Biol. (2015); 50(6):532-49.
- The Torsin Activator LULL1 Is Required for Efficient Growth of Herpes Simplex Virus 1. Turner EM, Brown RS, Laudermilch E, Tsai PL, Schlieker C. J Virol. (2015); 89(16):8444-52.
- The mechanism of Torsin ATPase activation Brown RS, Zhao C, Chase AR, Wang J, Schlieker C. Proc Natl Acad Sci U S A. (2014); 111(45):E4822-31
- Regulation of Torsin ATPases by LAP1 and LULL1. Zhao C, Brown RS, Chase AR, Eisele MR, Schlieker C. Proc Natl Acad Sci U S A (2013); 110(17):E1545-54.
- Alternative nuclear transport for cellular protein quality control. Rose A, Schlieker C. Trends Cell Biol. (2012); 22(10):509-14.
- Arresting a Torsin ATPase reshapes the endoplasmic reticulum. Rose AE, Zhao C, Turner EM, Steyer AM, Schlieker C. J Biol Chem. 289 (2014); (1):552-64.
- Tsai PL, Zhao C, Turner E, Schlieker C: The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. Elife. 2016 Jun 23; 2016 Jun 23.