Researchers at the University of Pennsylvania School of Medicine have discovered how a protein called Pmel17 is sorted by pigment cells in the skin and eye to make a fiber matrix that eventually sequesters melanin, the dark pigment found in skin, hair, and eyes. Understanding the molecular steps prior to fiber formation and when this process goes awry may lead to a better understanding of melanoma and Alzheimer's disease. Pmel17 is a major target within the immune system in current anti-melanoma immunotherapies. Michael S. Marks, PhD, Associate Professor of Pathology and Laboratory Medicine, and colleagues published their findings in the March issue of Developmental Cell.
Marks studies protein sorting determining how proteins are delivered to the correct organelle, or subcompartments, within the cell. He investigates this basic process in pigment cells, particularly sorting to the melanin storage compartment called the melanosome. Melanin is normally stored by the cell in melanosomes because its build-up outside the melanosome can lead to cell death.
In the pigment-producing cell, called the melanocyte, melanin is laid down on a fibrous matrix made from Pmel17. Other work from the Marks lab and collaborators showed that the structure of Pmel17 is similar to amyloid protein, one of the hallmarks of Alzheimer's disease plaques. Using mouse and human melanoma cells, the Marks lab also studies melanocytes for pathological conditions associated with mutations along the protein-sorting process.
"There's no evidence that Pmel17 per se will initiate pathological cellular structures, but recent research from our lab shows that if we look at the structure of the fibers made up of Pmel17, it has all the biophysical properties of amyloid," explains Marks. "Pmel17 is functioning in a physiological capacity the same way that amyloid functions in a pathological capacity."
Before the fibers are laid down, the researchers found in the DevelopmentalPage: 1 2 3 Related medicine news :1
Contact: Karen Kreeger
University of Pennsylvania School of Medicine
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