Baltimore, MD: How do cells get rid of mistakes? UMBI scientists, led by Dr. Mervyn J. Monteiro at the Medical Biotechnology Center, University of Maryland Biotechnology Institute in Baltimore, Maryland, have discovered a new protein that is an integral part of the pathway used by cells to get rid of misfolded proteins before they cause major problems. These kinds of problems are believed to be responsible for many human diseases including, Alzheimer's disease, Huntington's disease, cystic fibrosis, alpha 1-antitrypsin deficiency, congenital hypothyroidism, thyroglobin deficiency, osteogenesis imperfecta, albinism/tyrosinase deficiency, hypofibrinogenemia, and Pendred Syndrome to name a few.

As reported in an ePress article published in the Journal of Cell Science (J. Cell Sci. 2006; doi: 10.1242/jcs.03163), Dr. Monteiro and associates discovered a novel human protein, which they have called erasin, that functions like a molecular eraser, removing misfolded proteins from the endoplasmic reticulum (ER). The endoplasmic reticulum is the key cellular organelle where most functionally important proteins, such as receptors, are made. Failure to remove misfolded proteins from the ER, can clog up this chief protein synthesis apparatus, eventually leading to cell death. Earlier work had suggested that a molecular complex of many proteins exists in the ER to facilitate the removal and destruction of misfolded proteins by a process called ER-associated protein degradation (ERAD).

The photomicrograph above shows erasin in the ER.

While many of the proteins involved in ERAD in yeast and other organisms have been characterized, little is known about this process in humans. The newly discovered erasin is a key component of the human ERAD complex. The UMBI scientists together with their collaborators at the Nathan Kline Institute in New York have found it is required to remove misfolded proteins from the ER and that erasin protein levels were preferentially increased in the brains of people afflicted with Alzheimer's disease. The scientists speculate that the increase in erasin expression in Alzheimer's disease may reflect a preemptive and perhaps futile attempt by cells to get rid of toxic proteins from the brain. Thus, the identification of erasin could lead to a better understanding of Alzheimer's and new targets for intervention.

This research was funded by a grant to Dr. Monteiro from the National Institute of General Medical Sciences.

Written by Pamela Wright

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