A long-standing question concerns how stem cells maintain their identity through multiple divisions. Previously we reported that pre-existing and newly synthesized histone H3 are asymmetrically distributed during Drosophila male germline stem cell (GSC) asymmetric division. Here we show that phosphorylation at Threonine 3 of H3 (H3T3P) distinguishes preexisting versus newly synthesized H3. Converting T3 to the unphosphorylatable residue alanine (H3T3A) or to the phosphomimetic aspartate (H3T3D) disrupts asymmetric H3 inheritance. Expression of H3T3A or H3T3D specifically in early-stage germline also leads to cellular defects including GSC loss and germline tumors. Finally, compromising the activity of the H3T3 kinase Haspin enhances the H3T3A but suppresses the H3T3D phenotypes. Together these studies demonstrate that H3T3P distinguishes sister chromatids enriched with distinct pools of H3, coordinating asymmetric segregation of “old” H3 into GSCs, and that a tight regulation of H3T3 phosphorylation is required for male germline activity.
γ-Secretase cleaves amyloid precursor protein (APP) to produce Aβ peptide, and the secretase is a critical factor in the pathogenesis of Alzheimer’s Disease (AD), whereas acetylcholinesterase (AChE) is a key factor for maintaining normal nerve impulses. However, there has been no published research that focuses on the relationship between these two factors. γ-Secretase cleaves various substrates, and loss of function of γ-secretase is lethal. Thus, the mechanism by which γ-secretase cleaves APP is a key factor in AD pathogenesis. AChE is one of the main targets in the treatment of AD, and AChE inhibitors are commonly used for AD. Currently there is agreement that AChE inhibitors stabilizes acetylcholine (ACh) levels in the brain, which ensures ACh transport among neurons. However, the actual effect is limited. It has been reported that AChE interacts with PS1 and affects its glycosylation. This result suggests a link between AChE and γ-secretase. Here, we have tested the effects of AChE on cleavage of APP by γ-secretase.
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.