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Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis.

Harris KP, Tepass U - J. Cell Biol. (2008)

Bottom Line: Loss of Cdc42 function caused an increase in the endocytotic uptake of apical proteins, including apical polarity factors such as Crumbs, which are required for AJ stability.The Par complex acts as an effector for Cdc42 in controlling the endocytosis of apical proteins.This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.

ABSTRACT
Cell rearrangements require dynamic changes in cell-cell contacts to maintain tissue integrity. We investigated the function of Cdc42 in maintaining adherens junctions (AJs) and apical polarity in the Drosophila melanogaster neuroectodermal epithelium. About one third of cells exit the epithelium through ingression and become neuroblasts. Cdc42-compromised embryos lost AJs in the neuroectoderm during neuroblast ingression. In contrast, when neuroblast formation was suppressed, AJs were maintained despite the loss of Cdc42 function. Loss of Cdc42 function caused an increase in the endocytotic uptake of apical proteins, including apical polarity factors such as Crumbs, which are required for AJ stability. In addition, Cdc42 has a second function in regulating endocytotic trafficking, as it is required for the progression of apical cargo from the early to the late endosome. The Par complex acts as an effector for Cdc42 in controlling the endocytosis of apical proteins. This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs.

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Model of the Cdc42–Par complex function in the regulation of the apical endocytotic pathway. Our data suggest that Cdc42 and the Par complex cooperate to regulate two distinct steps in the endocytosis of apical membrane components. The Cdc42–Par complex inhibits endocytosis from the plasma membrane and also promotes progression from the early endosome (EE) to the multivesicular body/late endosome (MVB/LE). Apical and basolateral (including AJ) proteins follow distinct endocytotic routes.
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fig10: Model of the Cdc42–Par complex function in the regulation of the apical endocytotic pathway. Our data suggest that Cdc42 and the Par complex cooperate to regulate two distinct steps in the endocytosis of apical membrane components. The Cdc42–Par complex inhibits endocytosis from the plasma membrane and also promotes progression from the early endosome (EE) to the multivesicular body/late endosome (MVB/LE). Apical and basolateral (including AJ) proteins follow distinct endocytotic routes.

Mentions: Our findings support a model (Fig. 10) posing that Cdc42 regulates two distinct steps of endocytosis in Drosophila epithelial cells. Cdc42 function slows the removal of apical proteins from the plasma membrane by decreasing endocytotic uptake, and it accelerates the processing of apical cargo from the early to the late endosome. Previous work has suggested that Cdc42 might promote endocytosis through its effector Wasp and the regulation of actin polymerization (for review see Ridley, 2006). However, our observations that (a) embryos with compromised Par complex function show similar endocytotic defects as embryos with reduced Cdc42 function and that (b) endocytotic defects in embryos with compromised Cdc42 function can be rescued by the expression of an active form of aPKC indicate that the Par complex acts as an effector of Cdc42 to regulate endocytosis in the Drosophila ectodermal epithelium. The targets of aPKC in the endocytotic pathway are unknown at present, and we cannot rule out that they include actin regulators.


Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis.

Harris KP, Tepass U - J. Cell Biol. (2008)

Model of the Cdc42–Par complex function in the regulation of the apical endocytotic pathway. Our data suggest that Cdc42 and the Par complex cooperate to regulate two distinct steps in the endocytosis of apical membrane components. The Cdc42–Par complex inhibits endocytosis from the plasma membrane and also promotes progression from the early endosome (EE) to the multivesicular body/late endosome (MVB/LE). Apical and basolateral (including AJ) proteins follow distinct endocytotic routes.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2600741&req=5

fig10: Model of the Cdc42–Par complex function in the regulation of the apical endocytotic pathway. Our data suggest that Cdc42 and the Par complex cooperate to regulate two distinct steps in the endocytosis of apical membrane components. The Cdc42–Par complex inhibits endocytosis from the plasma membrane and also promotes progression from the early endosome (EE) to the multivesicular body/late endosome (MVB/LE). Apical and basolateral (including AJ) proteins follow distinct endocytotic routes.
Mentions: Our findings support a model (Fig. 10) posing that Cdc42 regulates two distinct steps of endocytosis in Drosophila epithelial cells. Cdc42 function slows the removal of apical proteins from the plasma membrane by decreasing endocytotic uptake, and it accelerates the processing of apical cargo from the early to the late endosome. Previous work has suggested that Cdc42 might promote endocytosis through its effector Wasp and the regulation of actin polymerization (for review see Ridley, 2006). However, our observations that (a) embryos with compromised Par complex function show similar endocytotic defects as embryos with reduced Cdc42 function and that (b) endocytotic defects in embryos with compromised Cdc42 function can be rescued by the expression of an active form of aPKC indicate that the Par complex acts as an effector of Cdc42 to regulate endocytosis in the Drosophila ectodermal epithelium. The targets of aPKC in the endocytotic pathway are unknown at present, and we cannot rule out that they include actin regulators.

Bottom Line: Loss of Cdc42 function caused an increase in the endocytotic uptake of apical proteins, including apical polarity factors such as Crumbs, which are required for AJ stability.The Par complex acts as an effector for Cdc42 in controlling the endocytosis of apical proteins.This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.

ABSTRACT
Cell rearrangements require dynamic changes in cell-cell contacts to maintain tissue integrity. We investigated the function of Cdc42 in maintaining adherens junctions (AJs) and apical polarity in the Drosophila melanogaster neuroectodermal epithelium. About one third of cells exit the epithelium through ingression and become neuroblasts. Cdc42-compromised embryos lost AJs in the neuroectoderm during neuroblast ingression. In contrast, when neuroblast formation was suppressed, AJs were maintained despite the loss of Cdc42 function. Loss of Cdc42 function caused an increase in the endocytotic uptake of apical proteins, including apical polarity factors such as Crumbs, which are required for AJ stability. In addition, Cdc42 has a second function in regulating endocytotic trafficking, as it is required for the progression of apical cargo from the early to the late endosome. The Par complex acts as an effector for Cdc42 in controlling the endocytosis of apical proteins. This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs.

Show MeSH
Related in: MedlinePlus