Disease relevance of kst

• We have isolated mutations in the gene encoding &bgr ;Heavy-spectrin in Drosophila, and have named this essential locus karst. karst mutant individuals have a pleiotropic phenotype characterized by extensive larval lethality and, in adult escapers, rough eyes, bent wings, tracheal defects and infertility [1].

High impact information on kst

• This is followed by the redistribution of beta Heavy-spectrin, a component of the membrane cytoskeleton, and by the ectopic deposition of cuticle and other apical components into these areas [2].
• Although Ankyrin is not required for the localization of the Spectrin skeleton to the neuromuscular junction, it contributes to Spectrin-mediated synapse development [3].
• Crumbs interacts with moesin and beta(Heavy)-spectrin in the apical membrane skeleton of Drosophila [4].
• Consistent with this hypothesis, we report that Crumbs is necessary for the organization of the apical SBMS in embryos and Schneider 2 cells, whereas the localization of Crumbs is not affected in karst mutants that eliminate the apical SBMS [4].
• We report that apical beta(Heavy)-spectrin (beta(H)), a terminal web protein that is also associated with the zonula adherens, is essential for normal epithelial morphogenesis of the Drosophila follicle cell epithelium during oogenesis [5].

Biological context of kst

• Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation [6].
• The phenotypes of the beta H spectrin mutations provide an exciting biological context in which to evaluate these roles and perhaps to uncover new ones [7].
• Beta heavy-spectrin has a restricted tissue and subcellular distribution during Drosophila embryogenesis [8].
• Here we establish that both the subcellular localization of the beta Heavy-spectrin protein and the tissue distribution of beta Heavy-spectrin transcript accumulation change dramatically during embryonic development [8].
• Genetic evidence is consistent with a negative role for Drosophila beta(Heavy)-spectrin in endocytosis, but the inhibitory mechanism has not been elucidated [9].

Anatomical context of kst

• Protein 4.1 functions to link transmembrane proteins with the underlying spectrin/actin cytoskeleton [10].
• A postsynaptic Spectrin scaffold defines active zone size, spacing, and efficacy at the Drosophila neuromuscular junction [3].
• Elimination of beta(H) by the karst mutation prevents apical constriction of the follicle cells during mid-oogenesis, and is accompanied by a gross breakup of the zonula adherens [5].
• Within karst mutant eyes, a significant number of ommatidia specifically lack photoreceptor R7 alongside more complex morphological defects [1].
• The distribution of beta Heavy-spectrin suggests roles in establishing an apicolateral membrane domain that is known to be rich in intercellular junctions and in establishing a unique membrane domain associated with contractile processes [8].

Associations of kst with chemical compounds

• Rhodamine phalloidin staining of karst mutant ovaries similarly reveals no conspicuous defect in the actin cytoskeleton or cellular morphology in egg chambers [1].

Co-localisations of kst

• Immunolocalization of betaHeavy-spectrin in wild-type eye-antennal and wing imaginal discs reveals that betaHeavy-spectrin is present in a restricted subdomain of the membrane skeleton that colocalizes with DE-cadherin [1].

Other interactions of kst

• This is in contrast to mutations in alpha-spectrin, the molecular partner of betaHeavy-spectrin, which affect cellular structure in both the larval gut and adult ovaries [1].
• Epistasis tests indicate that beta(Heavy)-spectrin is required during endocytosis after Dynamin and before Rab5-mediated endosome activities [11].
• In Drosophila, betaH-spectrin associates with the apical plasma membrane of epithelial cells; beta-spectrin is found at the lateral membrane [12].

References