Researchers from the Salk Institute for Biological Studies have been investigating on the lifespan of nuclear pore and how it influences their roles in the human body. Martin Hetzer, Ph.D., an assistant professor in the Salk's Molecular and Cell Biology Laboratory says that their findings can provide an explanation on how an aging cell changes and associates it to age related diseases.
Nuclear pores are large protein complexes that are assemble during cell division. It serves to store and organize genetic information and also functions as communication channels with the rest of the cell, exchanging proteins and RNA to and from a cell's nucleus. Nuclear pore complexes are important to both non-dividing and dividing cells. Cells that do not actively divide can cause implications for aging and age-related diseases.
Peripheral proteins attached to scaffold of the nuclear pore complexes are found to remain stable and intact throughout the lifespan of an organism and genes of these proteins are no longer active. This makes a big difference with the other proteins as most proteins turn over after a period of time. "If proteins are there, but transcripts of the information making the protein are no longer there, they have to be very stable," says Hetzer.
In aging cells, damaged proteins deteriorate the permeability of the barrier causing invasion of other molecules into the cytoplasm. Long term accumulation of damage in the stable nuclear pore complexes can weaken their function and affects cell homeostasis and survival which in directly plays a role in the aging process.
A cytoplasmic protein called tubulin, a type of long filaments that encompass a large part of the nucleus. These filaments are associated with several neurodegenerative diseases such as Parkinson's and are
found particularly in the substantia nigra of many Parkinson's patients. Substantia nigra is located in the midbrain that plays an important role in reward, addiction, and movement and involved in dopamine production and that is affected by the condition.
In conclusion, Hetzer and team states that the age-dependent defects in the scaffold proteins that weaken the nuclear pore’s permeability barrier. "We predict that when the permeability barrier is impaired, molecules are either lost from the nucleus or can leak into the nucleus and thereby change gene expression profiles," says Hetzer. "This could be a general aging mechanism, and it provides an explanation for the origin of these filaments, which have been known by pathologists for a long time."
In aging cells one of the proteins composing nuclear pores
becomes damaged and molecules that should be restricted to the cytoplasm invade the nucleus (outline shown in red). In particular, a protein called tubulin (shown in green), which is strictly a cytoplasmic protein, shows up as long filaments that co-opt a large part of the nucleus. (Credit: Courtesy of Dr. Maximiliano D'Angelo, Salk Institute for Biological Studies)
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