Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo
pathway |
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Authors: | Linda M Parsons Nicola A Grzeschik Melinda L Allott Helena E Richardson |
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Institution: | 1.Cell Cycle and Development; Peter MacCallum Cancer Centre; Melbourne, Victoria Australia;2.Department of Anatomy and Cell Biology; University of Melbourne; Melbourne, Victoria Australia;3.Department of Biochemistry and Molecular Biology University of Melbourne; Melbourne, Victoria Australia |
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Abstract: | A key goal of developmental biology is to understand the mechanisms that
coordinate organ growth. It has long been recognized that the genes that control
apico-basal cell polarity also regulate tissue growth. How loss of cell polarity
contributes to tissue overgrowth has been the subject of much speculation. Do
loss-of-function mutations in cell polarity regulators result in secondary
effects that globally deregulate cell proliferation, or do these genes
specifically control growth pathways? Three recent papers have shown that the
apico-basal polarity determinants Lgl/aPKC and Crb regulate tissue growth
independently of their roles in cell polarity and coordinately regulate cell
proliferation and cell death via the Salvador/Warts/Hippo (SWH) pathway.
Lgl/aPKC are required for the correct localization of Hippo (Hpo)/Ras associated
factor (RASSF), while Crb regulates the levels and localization of Expanded
(Ex), indicating that cell polarity determinants modify SWH pathway activity by
distinct mechanisms. Here, we review the key data that support these
conclusions, highlight remaining questions and speculate on the underlying
mechanisms by which the cell polarity complexes interact with the SWH pathway.
Understanding the interactions between cell polarity regulators and the SWH
pathway will improve our knowledge of how epithelial organization and tissue
growth are coordinated during development and perturbed in disease states such
as cancer.Key words: Drosophila, tumor suppressor gene, cell polarity, Hippo pathway, Crb, Lgl, aPKC |
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