Phosphorylation plays a significant role in a wide range of cellular processes. By adding a phosphate group to a protein or other molecule, phosphorylation turns many protein enzymes on and off, and thereby alters their function and activity.
The researchers also found that variations in ERK2 activity correlated with differences in L1 sensitivity to alcohol that they observed across cell lines and among different strains of mice. "Dou showed that he could take these cells that had been insensitive to alcohol for 13-14 years, and make them sensitive by ramping up the activity of this kinase" Charness said.
These variations suggest that genes for ERK2 and the signaling molecules that regulate ERK2 activity might influence genetic susceptibility to FASD. Moreover, their identification of a specific locus that regulates the alcohol sensitivity of L1 might facilitate the rational design of drugs that block alcohol neurotoxicity.
"The only thing this modification blocked was alcohol's ability to inhibit L1," Charness said. "If you're looking for a drug, ideally you're looking for it to block the effects of the toxin without interfering with the target molecule of the toxin."
The findings will also help guide an international consortium in its search for genes linked to families with fetal alcohol spectrum disorders.
"Prenatal alcohol exposure is the leading preventable cause of birth defects and developmental disorders in the United States," said Kenneth Warren, acting director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA),which supported the study. "These new findings are yet another important contribution from researchers who have been at the forefront of scientific discovery in FASD."
|Contact: David Cameron|
Harvard Medical School