- A conserved role for TOPBP1Dpb11 in DNA repair
The scaffold protein TOPBP1Dpb11 has been implicated in homologous recombination DNA repair, but its function and mechanism of action remain unclear. Liu et al. define a conserved role for TOPBP1Dpb11 in recombination control through regulated, opposing interactions with pro- and anti-resection factors.
- Importin-11: Tumor suppressor that maintains PTEN
Reduced PTEN protein is linked to tumorigenesis. Here, Chen et al. show that the nuclear transport receptor Importin-11 separates PTEN from degradation machinery. IPO11 mutant mice exhibit PTEN degradation, lung adenocarcinoma, and prostate neoplasia. In human prostatectomy patients, IPO11 status predicts disease recurrence and metastasis.
- Defects in phagocytosis in dFmr1 mutants
Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. Here, O’Connor et al. find that Drosophila Fmr1 mutants, a model for Fragile X syndrome, exhibit defects in phagocytosis by innate immune cells in both the body and the brain.
- Dendritic loss of selective neuronal types
Mitochondrial dysfunction is associated with neuropathological events, but how it mediates loss of specific neuronal subtypes is unclear. Tsuyama et al. show that mitochondrial dysfunction triggers selective dendritic loss in class IV arborization neurons in a manner dependent on eIF2α phosphorylation and translation inhibition.
- Role of eIF2α in dendritic degeneration
Xin Qi previews work by Tsuyama and colleagues linking eIF2α phosphorylation-mediated control of translation with neuronal subtype-specific mitochondrial stress-induced dendritic branching defects.
- Osteoblastic Lrp4 regulates osteoclastogenesis
Lrp4 is mutated in patients with high-bone-mass diseases. Loss of Lrp4 in osteoblasts (OBs) increases bone formation by OBs and decreases bone resorption by osteoclasts through an unclear mechanism. Xiong et al. show that overproduction of extracellular adenosine in Lrp4-deficient OBs, which are derived from ATP hydrolysis and signals through A2AR and RANK, may underlie Lrp4 regulation of osteoclastogenesis.