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22 June 2008 No Comment

Miniature Hairless gene from honey bee is enough to block notch signaling in Drosophila

Notch Signaling:
Notch signaling pathway is implicated in various developmental process in all eumetazoans,required at different developmental stages in various tissues.In Drosophila,Notch pathway is activated by binding of ligands Serrate and Delta which results in cleaving of Notch intracellular domain.Once cleaved the intra cellular domain is free to enter nucleus and there with the help of suppressor of Hairless (Su(H) and mastermind forms a activator complex.Notch receptor with co activators (Su(H) and mastermind activates downstream target genes in context depending manner.

Hairless another protein in flies, acts as a negative regulator of Notch pathway.This is achieved with the help of other co repressors proteins like Groucho and C-terminal binding protein (CtBP), which then converts Su(H) into a repressor of the Notch target genes.It’s not a surprise to see conservation among players of Notch pathway between vertebrates and invertebrates owing to importance of Notch signaling in eumetazoans.But one exception to this is “Hairless”which doesnot have a vertebrate homolog.

Hairless protein in Apis mellifera:

The search of vertebrate homolog of hairless lead us to the latest article in BMC EVOLUTIONARY BIOLOGY by Dieter Maier et al ,where they show that smaller version of Hairless gene in Apis mellifera (Honey bee) functions as a potent inhibitor of Notch signaling in Drosophila and also rescues loss of function mutants of Hairless.The orthologous proteins are only 54% identical, and Apis Hairless is only about 36% of the size of Drosophila. Despite the small size, Apis Hairless contains the characteristic interaction domains and is able to bind to the Drosophila proteins Su(H), Gro, CtBP and Pros26.4 as does Drosophila Hairless.
Image showing over expression of Hairless from Apis affecting adult wing and Vg BE down regulation.
Image Credit :
Dieter Maier , Anna X Chen , Anette Preiss and Manuela Ketelhut.
The tiny Hairless protein from Apis mellifera: a potent antagonist of Notch signaling in Drosophila melanogaster.
BMC Evolutionary Biology 2008, 8:175doi:10.1186/1471-2148-8-175

It is not clear whether Hairless also acts as inhibitor of Notch pathway in Apis mellifera as genetics experiments are not possible like in Drosophila but authors predict that it could be the case as they found single orthologues of Notch, Su(H), Gro and CtBP that are extremely well conserved in Apis,and one reasonably well conserved Mastermind orthologue.Authors also strongly believe that rapid evolution of Hairless protein has also led to its escape from identification in groups other than insects.This experimental approach is to eventually identify such a homologue and to analyze the H structure in detail to characterize important functional domains. The H orthologue from the honeybee will help us in this process.To conclude authors have shown that A.m.H functions as a bone fide Notch antagonist in the fly despite considerable divergence with regard to size and amino acid sequence,which will help to understand Hairless like proteins in other species and decipher more about Notch repressor-complexes that down-regulate Notch signaling in other Metazoans.

Reference:

Dieter Maier , Anna X Chen , Anette Preiss and Manuela Ketelhut.
The tiny Hairless protein from Apis mellifera: a potent antagonist of Notch signaling in Drosophila melanogaster.
BMC Evolutionary Biology 2008, 8:175doi:10.1186/1471-2148-8-175


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