No abstract

Kugelkern is so far the first nuclear protein, except for lamins, that contains a farnesylation site. Our findings suggest that Kugelkern is a rate-determining factor for nuclear size increase. We propose that association of farnesylated Kugelkern with the inner nuclear membrane induces expansion of nuclear surface area, allowing nuclear growth.

SummaryThe nuclear lamina consists of a meshwork of lamins and lamina-associated proteins, which provide mechanical support, control size and shape of the nucleus, and mediate the attachment of chromatin to the nuclear envelope. Abnormal nuclear shapes are observed in aging cells of humans and nematode worms. The expression of laminΔ Δ Δ Δ 50 , a constitutively active lamin A splicing variant in Hutchinson-Gilford progeria syndrome patients, leads to the lobulation of the nuclear envelope accompanied by DNA damage, and loss of heterochromatin. So far, it has been unclear whether these age-related changes are laminΔ Δ Δ Δ 50 specific or whether proteins that affect nuclear shape such as KUGELKERN or LAMIN B in general play a causative role in senescence. Here we show that in adult Drosophila flies, the size of the nuclei increases with age and the nuclei assume an aberrant shape. Moreover, induced expression of the farnesylated lamina proteins Lamin B and Kugelkern cause aberrant nuclear shapes and reduce the lifespan of adult flies. The shorter lifespan correlates with an early decline in age-dependent locomotor behaviour. Expression of kugelkern or lamin B in mammalian cells induces a nuclear lobulation phenotype in conjunction with DNA damage, and changes in histone modification similar to that found in cells expressing laminΔ Δ Δ Δ 50 or in cells from aged individuals. We conclude that lobulation of the nuclear membrane induced by the insertion of farnesylated lamina-proteins can lead to aging-like phenotypes.

Queen health is crucial to colony survival of honeybees, since reproduction and colony growth rely solely on the queen. Queen failure is considered a relevant cause of colony losses, yet few data exist concerning effects of environmental stressors on queens. Here we demonstrate for the first time that exposure to field-realistic concentrations of neonicotinoid pesticides can severely affect the immunocompetence of queens of western honeybees (Apis mellifera L.). In young queens exposed to thiacloprid (200 µg/l or 2000 µg/l) or clothianidin (10 µg/l or 50 µg/l), the total hemocyte number and the proportion of active, differentiated hemocytes was significantly reduced. Moreover, functional aspects of the immune defence namely the wound healing/melanisation response, as well as the antimicrobial activity of the hemolymph were impaired. Our results demonstrate that neonicotinoid insecticides can negatively affect the immunocompetence of queens, possibly leading to an impaired disease resistance capacity.