High impact information on scrib

• We used analysis of variance to partition variation in transcript abundance between males and females and between smi genotypes and to determine the genotype-by-sex interaction [1].
• Mutations in Drosophila scribble (scrib), which encodes a multi-PDZ (PSD-95, Discs-large and ZO-1) and leucine-rich-repeat protein, cause aberrant cell shapes and loss of the monolayer organization of embryonic epithelia [2].
• Loss of scrib function results in the misdistribution of apical proteins and adherens junctions to the basolateral cell surface, but basolateral protein localization remains intact [2].
• Scrib is localized to the epithelial septate junction, the analogue of the vertebrate tight junction, at the boundary of the apical and basolateral cell surfaces [2].
• We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia, and that scrib also acts as a tumor suppressor [3].

Biological context of scrib

• Finally, alternative splicing of scrib generates transcripts that differ in the number of leucine-rich repeats and PDZ domains [4].
• We found that the transposon in this line is located between the predicted promoter region and the transcription initiation site of scrib [4].
• The tumour suppressor gene scribble (scrib) is required for epithelial polarity and growth control in Drosophila [5].
• The molecular mechanisms by which Dlg, Scrib and Lgl proteins regulate cell proliferation are not clear, but there is some evidence that epithelial polarisation is required for this regulation [6].
• Drosophila lethal giant larvae: (lgl), discs large (dlg) and scribble (scrib) are tumour suppressor genes acting in a common pathway, whose loss of function leads to disruption of cell polarity and tissue architecture, uncontrolled proliferation and growth of neoplastic lesions [7].

Anatomical context of scrib

• In addition, FM1-43 imaging of recycling synaptic vesicles shows that vesicle dynamics are impaired in scrib mutants [8].
• The Drosophila tumor suppressor Scribble (Scrib) is a PDZ-containing protein required for maintaining epithelial cell polarity [8].
• At the larval neuromuscular junction, Scrib colocalizes and indirectly interacts with another tumor suppressor and PDZ protein, Discs-Large (Dlg) [8].
• Possible tube-size functions of septate junctions include patterning of the apical extracellular matrix and regulation of conserved cell polarity genes such as Scribble and Discs Large [9].
• Expression of Scrib is widespread in olfactory organs and the central nervous system [4].

Co-localisations of scrib

• We also show that at Drosophila synapses DLG colocalizes with SCRIB and that this colocalization is likely to be mediated by direct interactions between GUKH and the PDZ2 domain of SCRIB [10].

Other interactions of scrib

• Previously, we identified through P[lArB]-element mutagenesis a smell impaired (smi) mutant, smi21F, with odorant-specific defects in avoidance responses [11].
• scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila [12].

Analytical, diagnostic and therapeutic context of scrib

• Quantitative complementation tests of mutations at these coregulated genes with the smi mutations showed that in most cases (67%) epistatic interactions for olfactory behavior mirrored epistasis at the level of transcription, thus identifying new candidate genes regulating olfactory behavior [1].

References