Disease relevance of sbb

• In brakeless mutants, R1-R6 growth cones frequently fail to terminate migration in their normal target, the lamina, and instead project through it and terminate in the second optic ganglion, the medulla [1].

High impact information on sbb

• The Sdt-containing Crb complex is recruited apically by the Baz complex to counter antagonistic Scrib activity [2].
• Genetic screens of Drosophila melanogaster embryos have identified three complexes, each containing one of the PDZ domain proteins--Stardust (Sdt), Bazooka (Baz) and Scribble (Scrib)--that control epithelial polarity and formation of zonula adherens [2].
• Thus, a finely tuned balance between Scrib and Crb complex activity sets the limits of the apical and basolateral membrane domains and positions cell junctions [2].
• The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin [3].
• Using an allelic series of mutations along with rescuing transgenes, we have identified domain requirements for polarity, proliferation control, and other Scrib functions [4].

Biological context of sbb

• The vital function of sbb was restored by ubiquitous expression of this transgene throughout development [5].
• In Drosophila imaginal discs, loss of the neoplastic tumor suppressor gene scribble (scrib), which encodes a multidomain scaffolding protein, disrupts epithelial organization and also causes unchecked proliferation [4].
• Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble [4].
• Human homolog of Drosophila tumor suppressor Scribble negatively regulates cell-cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial cells [6].

Anatomical context of sbb

• In contrast, expression of this sbb transcript in motoneurons, sensory neurons or large numbers of unidentified interneurons was not sufficient [7].
• The leucine-rich repeats (LRR) tether Scrib to the plasma membrane, are both necessary and sufficient to organize a polarized epithelial monolayer, and are required for all proliferation control [4].
• Target selection decisions of the R1-R6 subset of photoreceptor axons have been found to be influenced by the nuclear factors Brakeless and Runt, and target selection decisions of the R7 subset of axons have been found to require the cell-surface proteins Ptp69d, Lar and N-cadherin [8].
• Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression [9].

Other interactions of sbb

• In this report, we demonstrate that mtv integrates the activities of En and Hh that shape tkv expression pattern [10].
• Thus, mtv plays a key part of regulatory mechanism that makes the activity gradient of the Dpp morphogen [10].
• Here we demonstrate strong genetic interactions between gro and Atro and also with mutations in a third gene, scribbler (sbb), which encodes a nuclear protein of unknown function [11].

Analytical, diagnostic and therapeutic context of sbb

• Our genetic dissection of behavior has isolated scribbler (sbb), a vital gene that encodes a novel protein expressed in the embryonic and larval nervous systems and in the imaginal discs [5].

References