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Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble.

Zeitler J, Hsu CP, Dionne H, Bilder D - J. Cell Biol. (2004)

Bottom Line: The PDZ domains, which recruit the LRR to the junctional complex, are dispensable for overall epithelial organization.PDZ domain absence leads to mild polarity defects accompanied by moderate overproliferation, but the PDZ domains alone are insufficient to provide any Scrib function in mutant discs.We suggest a model in which Scrib, via the activity of the LRR, governs proliferation primarily by regulating apicobasal polarity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.

ABSTRACT
Cell polarity and cell proliferation can be coupled in animal tissues, but how they are coupled is not understood. 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. Using an allelic series of mutations along with rescuing transgenes, we have identified domain requirements for polarity, proliferation control, and other Scrib functions. 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. The PDZ domains, which recruit the LRR to the junctional complex, are dispensable for overall epithelial organization. PDZ domain absence leads to mild polarity defects accompanied by moderate overproliferation, but the PDZ domains alone are insufficient to provide any Scrib function in mutant discs. We suggest a model in which Scrib, via the activity of the LRR, governs proliferation primarily by regulating apicobasal polarity.

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Size control in scrib wing discs. Single confocal sections of phalloidin stained wing discs are shown. When compared with WT (A), all scrib alleles show increased size (B, scrib 2; C, scrib 3; D, scrib 4; E, scrib 5; F, scrib j7B3). G quantitates the degree of wing disc cell overproliferation in the mutant alleles and transgene rescues, normalized to WT. Bars indicate SDs.
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fig2: Size control in scrib wing discs. Single confocal sections of phalloidin stained wing discs are shown. When compared with WT (A), all scrib alleles show increased size (B, scrib 2; C, scrib 3; D, scrib 4; E, scrib 5; F, scrib j7B3). G quantitates the degree of wing disc cell overproliferation in the mutant alleles and transgene rescues, normalized to WT. Bars indicate SDs.

Mentions: We next assayed the ability of the mutant Scrib proteins to control cell proliferation in the wing disc. Confocal sections reveal an increase in both surface area and volume of mutant discs when compared with wild type (WT). The size difference is most dramatic for the multilayered discs of scrib 1, 2, and 3 animals, intermediate for scrib 4 and 5 and very slight for scrib 6 and 7 (Fig. 2, A–E). To exclude differences in cell shape or tissue organization and quantitatively assay proliferation, cell counts on dissociated discs were performed (Fig. 2 G). These counts reveal that the unpolarized tissue of scrib 3 animals contains ∼500% as many cells as WT, an increase similar to scrib 1 (Bilder et al., 2000). In the polarized discs of scrib 4 animals, a ∼300% increase is evident, indicating that scrib cells that form polarized epithelial monolayers can nevertheless be partially defective in proliferation control.


Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble.

Zeitler J, Hsu CP, Dionne H, Bilder D - J. Cell Biol. (2004)

Size control in scrib wing discs. Single confocal sections of phalloidin stained wing discs are shown. When compared with WT (A), all scrib alleles show increased size (B, scrib 2; C, scrib 3; D, scrib 4; E, scrib 5; F, scrib j7B3). G quantitates the degree of wing disc cell overproliferation in the mutant alleles and transgene rescues, normalized to WT. Bars indicate SDs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172630&req=5

fig2: Size control in scrib wing discs. Single confocal sections of phalloidin stained wing discs are shown. When compared with WT (A), all scrib alleles show increased size (B, scrib 2; C, scrib 3; D, scrib 4; E, scrib 5; F, scrib j7B3). G quantitates the degree of wing disc cell overproliferation in the mutant alleles and transgene rescues, normalized to WT. Bars indicate SDs.
Mentions: We next assayed the ability of the mutant Scrib proteins to control cell proliferation in the wing disc. Confocal sections reveal an increase in both surface area and volume of mutant discs when compared with wild type (WT). The size difference is most dramatic for the multilayered discs of scrib 1, 2, and 3 animals, intermediate for scrib 4 and 5 and very slight for scrib 6 and 7 (Fig. 2, A–E). To exclude differences in cell shape or tissue organization and quantitatively assay proliferation, cell counts on dissociated discs were performed (Fig. 2 G). These counts reveal that the unpolarized tissue of scrib 3 animals contains ∼500% as many cells as WT, an increase similar to scrib 1 (Bilder et al., 2000). In the polarized discs of scrib 4 animals, a ∼300% increase is evident, indicating that scrib cells that form polarized epithelial monolayers can nevertheless be partially defective in proliferation control.

Bottom Line: The PDZ domains, which recruit the LRR to the junctional complex, are dispensable for overall epithelial organization.PDZ domain absence leads to mild polarity defects accompanied by moderate overproliferation, but the PDZ domains alone are insufficient to provide any Scrib function in mutant discs.We suggest a model in which Scrib, via the activity of the LRR, governs proliferation primarily by regulating apicobasal polarity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.

ABSTRACT
Cell polarity and cell proliferation can be coupled in animal tissues, but how they are coupled is not understood. 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. Using an allelic series of mutations along with rescuing transgenes, we have identified domain requirements for polarity, proliferation control, and other Scrib functions. 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. The PDZ domains, which recruit the LRR to the junctional complex, are dispensable for overall epithelial organization. PDZ domain absence leads to mild polarity defects accompanied by moderate overproliferation, but the PDZ domains alone are insufficient to provide any Scrib function in mutant discs. We suggest a model in which Scrib, via the activity of the LRR, governs proliferation primarily by regulating apicobasal polarity.

Show MeSH
Related in: MedlinePlus