minibrain

Regulation

The DYRKs (dual specificity tyrosine phosphorylation-regulated kinases) are a conserved family of protein kinases that autophosphorylate a tyrosine residue in their activation loop by an intra-molecular mechanism and phosphorylate exogenous substrates on serine/threonine residues. Little is known about the identity of true substrates for DYRK family members and their binding partners. To address this question, full-length dDYRK2 (Drosophila DYRK2) was used as bait in a yeast two-hybrid screen of a Drosophila embryo cDNA library. Of 14 independent dDYRK2 interacting clones identified, three were derived from the chromatin remodelling factor, SNR1 (Snf5-related 1), and three from the essential chromatin component, TRX (trithorax). The association of dDYRK2 with SNR1 and TRX was confirmed by co-immunoprecipitation studies. Deletion analysis showed that the C-terminus of dDYRK2 modulated the interaction with SNR1 and TRX. DYRK family member MNB (Minibrain) was also found to co-precipitate with SNR1 and TRX, associations that did not require the C-terminus of the molecule. dDYRK2 and MNB were also found to phosphorylate SNR1 at Thr102 in vitro and in vivo. This phosphorylation required the highly conserved DH-box (DYRK homology box) of dDYRK2, whereas the DH-box was not essential for phosphorylation by MNB. This is the first instance of phosphorylation of SNR1 or any of its homologues and implicates the DYRK family of kinases with a role in chromatin remodelling (Kinstrie, 2006. Full text of article).

DEVELOPMENTAL BIOLOGY

Protein extracts of embryos and pupae contain consistently more Mnb protein A and C than those of third instar larvae and adults. By contrast, Mnb protein B appears to be expressed most markedly in third instar larvae and pupae. In addition, Mnb protein B is the most prominent of the three in third instar larvae (Tejedor, 1995).

Embryonic

In late embryos, MNB mRNA is expressed in the ventral cord and in the brain, but not in the peripheral nervous system. Also, MNB mRNA is not detected in embryonic neuroblasts (Tejedor, 1995).

Larval

Anti Mnb antibodies stain most prominently the mushroom body neuropil and the opc of the optic lobes. Thus mnb appears to be expressed prominently in larval tissue where neuronal progeny are generated during post-embryonic development. Strikingly, the level of protein is low in adult optic lobes and central brain hemispheres (Tejedor, 1995)

Adult

The level of Mnb protein is low in adult optic lobes and central brain hemespheres but relatively high in retinal pigment cells and in the alpha, beta and gama lobes and peduncle of the mushroom bodies (Tejedor, 1995).

Effects of mutation or deletion

Four alleles of minibrain have been described. The external appearance of mutant flies, including body and sensory organs, is nearly indistinguishable from wild type. The mutants are slightly smaller in size and require about 10% more time for their development; they also have considerable difficulties escaping from their pupal case. The brains of adult mutant flies are greatly reduced in size but shows no gross alterations in neuronal architecture. Major size reductions are seen in the optic lobes (50%-70%), most markedly in the lobula complex and in the central brain (40%-50%). The marked reduction of the lobula complex is probably also the reason for the increased curvature of the medulla in mnb mutants. The central brain hemispheres are reduced mainly in their ventral to dorsal and, respectively, anterior and posterior extensions. Axon bundles that project from the lobula complex to the lateral protocerebrum (optic stalk) are visibly thinner in the mutants. The number of anterior optic tract fibers is reduced by about 70%, and the number of cervical connective fibers is reduced by about 30%. Eyes appear normal (Tejedor, 1995).

Freely walking mutant flies cannot fixate a pattern in an area test. Wild type flies are attracted by a vertical dark stripe surrounded by an illuminated translucent area, while mutant flies have lost this preference. Odor discrimination is poor. Although locomotor activity of freely walking animals is low, optomotor turning behavior of mutant males walking on a styrofoam ball and motion-induced landing responses are normal.

minibrain mutant larvae develop normally into the third instar. Mutations cause an abnormal spacing of neuroblasts in the outer proliferation center (opc) of larval brain, with the implication that mnb opc neuroblasts produce less neuronal progeny than do wild type. As a consequence, the adult mnb brain exhibits a specific and marked size reduction of the optic lobes and central brain hemispheres. The insufficient number of distinct neurons in mnb brains is correlated with specific abnormalities in visual and olfactory behavior, although eye and antennal morphology are normal (Tejedor, 1995).

The influence of mutations in seven neurological genes on the number of fibers in the anterior optic tract (AOT) of Drosophila melanogaster has been investigated. The number of fibers in the AOT can be drastically reduced in single and especially in multiple mutants. However, no evidence for synergistic interactions between the sample of mutations used in any of the genes examined (sine oculis , reduced optic lobes, minibrain, and small optic lobes) was obtained at the level of the AOT. The rolKS222 and so mutations eliminate similar fiber sets in the AOT, which are distinctly different from those eliminated by solKS58 and mnb1 (Hoube, 1992).

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date revised: 30 October 2009 

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