Scientists have discovered an interaction between two key proteins that help regulate and maintain cells producing neurons that may offer insight into mental illness or age-related disease. The paper was written by Salk Institute scientists led by Rusty Gage, a professor in Salk's Laboratory of Genetics, and published yesterday in Cell Stem Cell.
The researchers were seeking to understand aspects of neurogenesis in adult brains, specifically how neural precursor cells maintain their cellular identity as they divide and create neurons or astrocytes. The team already knew that different genes were expressed in the nucleus of each of the three cell types. They also drew from a previous study by Salk professor and coauthor of the paper Martin Hetzer, which found that proteins in the nuclear membrane influence gene expression in different kinds of cancer cells. Working together, the two teams explored whether something similar may be happening in brain cells.
To do this, the researchers conducted screens in mouse and rat cells to determine which genes were being transcribed into proteins in precursor cells, immature neurons and astrocytes. The precursors were found to contain a high number of Nup153, which is part of a multiprotein complex that makes up part of a gatekeeping pore in the nuclear membrane. Immature neurons had an intermediate level of Nup153, and astrocytes had the lowest level.
Based on this information, and the fact that all three cell types had the same number of pores, the team concluded that Nup153 levels influenced cell type. Disruption of Nup153 function was found to trigger differentiation in precursor cells.
Knowing that Nup153 levels are also high in cells with elevated levels of Sox2, the team fluorescently tagged Nup153 and Sox2 in the different cell types, revealing interaction between the two transcription factors. The next steps are to explore interaction between the pore complex and other transcription factors that affect neuronal function, in hopes of better understanding neurological disorders.
Image: Salk scientists find that interaction between two key proteins regulates development of neurons. A fluorescent microscopy image shows Nup153 (red) in pore complexes encircling and associating with Sox2 (green) in a precursor cell nucleus. Image courtesy of Salk Institute/Waitt Center.