Developmental and loco-like effects of a swainsonine-induced inhibition ofα-mannosidase in the honey bee,Apis mellifera.
BACKGROUND
Deficiencies in lysosomal a-mannosidase (LAM) activity in animals, caused either by mutations or by consuming toxic alkaloids, lead to severe phenotypic and behavioural consequences. Yet, epialleles adversely affecting LAM expression exist in the honey bee population suggesting that they might be beneficial in certain contexts and cannot be eliminated by natural selection.


METHODS
We have used a combination of enzymology, molecular biology and metabolomics to characterise the catalytic properties of honey bee LAM (AmLAM) and then used an indolizidine alkaloid swainsonine to inhibit its activityin vitroandin vivo.


RESULTS
We show that AmLAM is inhibitedin vitroby swainsonine albeit at slightly higher concentrations than in other animals. Dietary exposure of growing larvae to swainsonine leads to pronounced metabolic changes affecting not only saccharides, but also amino acids, polyols and polyamines. Interestingly, the abundance of two fatty acids implicated in epigenetic regulation is significantly reduced in treated individuals. Additionally, swainsonie causes loco-like symptoms, increased mortality and a subtle decrease in the rate of larval growth resulting in a subsequent developmental delay in pupal metamorphosis.


CONCLUSIONS
We consider our findings in the context of cellular LAM function, larval development, environmental toxicity and colony-level impacts. The observed developmental heterochrony in swainsonine-treated larvae with lower LAM activity offer a plausible explanation for the existence of epialleles with impaired LAM expression. Individuals carrying such epialleles provide an additional level of epigenetic diversity that could be beneficial for the functioning of a colony whereby more flexibility in timing of adult emergence might be useful for task allocation.
Research School of Biology, Australian National University , Canberra , Australia.
Laura
L
Wedd
Research School of Biology, Australian National University, Canberra, Australia; Centre for Research in Therapeutic Solutions, Health Research Institute, Faculty of Education, Science, Technology and Mathematics, University of Canberra, Canberra, Australia.
Regan
R
Ashby
Research School of Biology, Australian National University , Canberra , Australia.
Sylvain
S
Foret
Research School of Biology, Australian National University , Canberra , Australia.
Ryszard
R
Maleszka
Deleterious epialleles; Epigenetic variation; Mannosidosis; Metabolism; Toxic alkaloid