In the moss, they were very nearly interchangeable, Quatrano said. This suggested that presenilin has a role outside the Notch pathway and may provide clues in mammalian systems as to its primary role, independent of its substrate in mammalian cells.
We were amazed to realize that genes from moss and humans were not only structurally conserved but also shared similar functions, Khandelwal said.
Moonlighting protein in mammals
We spent a lot of time trying to find an activity of PS to circumvent cleavage of APP, which has been very difficult, Kopan said. Importantly, the human protein acted in plant cells even if its enzymatic activity was removed by mutation. We stumbled upon an observation that presenilin proteins in mammals can perform other functions besides the enzymatic ones, that is, outside its role as gamma secretase. Were now looking closely to define this moonlighting functions and determine their contribution to disease.
In moss, the mutant phenotypes suggest presenilin might play a role in signal gathering, cytoskeleton organization and/or cell wall composition and organization. Quatrano and Khandelwal are checking that out. Kopan, Chandu and others are searching for presenilins moonlighting activities in mammalian cells.
As a developmental biologist, my job is to translate the genetic code as if it were a manufacturers manual, and that is accomplished by gaining detailed understanding of genes and protein function, Kopan said. Un
|Contact: Tony Fitzpatrick|
Washington University in St. Louis