Progerin's 'discrimination' may contribute to fatal disease HGPS

May 06, 2013
A new study in The Journal of Cell Biology suggests that the fatal disease HGPS might result from the selective exclusion of large proteins or protein complexes from the nucleus. One such protein, Tpr (red), accumulates in the nuclei of cells from a healthy person (left), but it remains in the cytoplasm of cells from an HGPS patient (right). Credit: Snow, C.J., et al. 2013. J. Cell Biol. doi:10.1083/jcb.201212117

A mutant protein responsible for Hutchinson-Gilford Progeria syndrome (HGPS) bars large proteins from entering the nucleus, according to a study in The Journal of Cell Biology.

The culprit in HGPS, a fatal disease that resembles , is a protein variant called Progerin. This defective protein impairs cells in many ways, including reducing nuclear levels of the RanGTPase. Ran is crucial for nuclear import and export, as it stimulates unloading of cargo that has just entered the nucleus and loading of cargo that's ready to exit. Progerin also impedes the import of Tpr, which forms the basket-like structure on the inner side of nuclear pores. But the mechanism behind this exclusion wasn't clear.

One possibility is that Progerin disrupts the activity of Tpr's sequence (NLS). To test this idea, a team led by researchers from the University of Virginia replaced Tpr's NLS with the localization sequence from a protein that readily enters the nucleus. The modified Tpr was still locked out, however, suggesting that the effect wasn't related to its NLS.

Tpr is one of the largest proteins to traverse . The researchers found that Progerin also limits the nuclear import of three other hefty proteins. This size effect stems from the reduction in nuclear Ran levels triggered by Progerin. For reasons that are still unclear, large cargoes require more Ran to enter the nucleus. These findings suggest that some cellular defects of HGPS might result from the exclusion of large cargoes, such as multisubunit enzyme complexes, from the nucleus.

Explore further: How steroid hormones enable plants to grow

add to favorites email to friend print save as pdf

Related Stories

Possible new drug for children with progeria

Jun 30, 2011

(Medical Xpress) -- A new study published in the journal Science Translational Medicine shows that rapamycin and its derivative everolimus, which is currently used to treat cancer and transplant rejections, may wo ...

Genetic disease linked to protein build-up

Aug 29, 2012

Mutations of the gene Lmna previously thought to be directly responsible for a group of laminopathies—serious developmental conditions including premature aging and a form of muscular dystrophy—in fact ...

New insight into 'accelerated aging' disease

Sep 13, 2010

Hutchinson-Gilford Progeria Syndrome (HGPS or progeria) is a rare genetic disease that causes young children to develop symptoms associated with advanced age, such as baldness, wrinkles, osteoporosis and cardiovascular disease. ...

Recommended for you

Researchers discover new strategy germs use to invade cells

10 hours ago

The hospital germ Pseudomonas aeruginosa wraps itself into the membrane of human cells: A team led by Dr. Thorsten Eierhoff and Junior Professor Dr. Winfried Römer from the Institute of Biology II, members of the Cluster ...

Progress in the fight against harmful fungi

10 hours ago

A group of researchers at the Max F. Perutz Laboratories has created one of the three world's largest gene libraries for the Candida glabrata yeast, which is harmful to humans. Molecular analysis of the Candida ...

How steroid hormones enable plants to grow

Aug 19, 2014

Plants can adapt extremely quickly to changes in their environment. Hormones, chemical messengers that are activated in direct response to light and temperature stimuli help them achieve this. Plant steroid ...

Surviving the attack of killer microbes

Aug 19, 2014

The ability to find food and avoid predation dictates whether most organisms live to spread their genes to the next generation or die trying. But for some species of microbe, a unique virus changes the rules ...

Histones and the mystery of cell proliferation

Aug 19, 2014

Before cells divide, they create so much genetic material that it must be wound onto spools before the two new cells can split apart. These spools are actually proteins called histones, and they must multiply ...

User comments : 0