Autism Linked to Egg Cells’ Difficulty Creating Large Proteins

New work from Carnegie’s Ethan Greenblatt and Allan Spradling reveals that the genetic factors underlying fragile X syndrome, and potentially other autism-related disorders, stem from defects in the cell’s ability to create unusually large protein structures.

Expanding their analysis, Greenblatt and Spradling revealed that Fmr1 mutant egg cells produce reduced amounts of several hundred proteins, many of which, if missing completely, are associated with autism. 

A common denominator among the affected proteins is that they encode some of the largest proteins constructed by our bodies.  Even in normal eggs, large proteins, including those affected by Fmr1, are produced inefficiently, reflecting the challenge of stringing together a very long protein chain under conditions of RNA storage.

“We think that Fmr1 serves as a sort of a helper, which boosts the production of critically important large proteins that are difficult for eggs or neurons to manufacture,” Greenblatt said. “Without Fmr1, egg cells have inadequate supplies of specific large proteins and prematurely start to fail. Since Fmr1 is also important in the brain, the loss of certain large proteins associated with autism could explain the autism-like symptoms of fragile X syndrome patients.”

Future research should investigate whether problems related to the manufacture of large proteins is linked to aging or other disorders such as Alzheimer’s disease and ALS.

 


This research was funded by the Jane Coffin Childs Memorial Fund and the Howard Hughes Medical Institute.

Autism Linked to Egg Cells’ Difficulty Creating Large Proteins // Allan Spradling & Ethan Greenblatt