Journal of Molecular Biology
ReviewThe Scribble Cell Polarity Module in the Regulation of Cell Signaling in Tissue Development and Tumorigenesis
Graphical Abstract
Section snippets
Introduction: Cell polarity regulation and tumorigenesis
Cell polarity involves the asymmetric distribution of macromolecules to specific membrane domains, which is essential for normal cellular function and morphogenesis during development in multicellular organisms [1], [2], [3], [4], [5], [6], [7]. There are four main types of cell polarity: 1) apico-basal cell polarity (ABCP, epithelial polarity) [1], [6], [7], [8], 2) planar cell polarity (PCP, polarity across the plane of an epithelium) [9], [10], [11], 3) asymmetric cell division (ACD, which
Scribble module protein structure and function
Although the Scrib, Dlg and Lgl proteins do not have intrinsic enzymatic activity, they all contain a number of well-characterized protein–protein interaction domains (described in more detail below) that enables them to bind to signaling proteins, such as kinases and phosphatases. Importantly, their function appears to be absolutely dependent on their cellular sublocalization. Hence, much of the currently known functions of the Scribble module proteins can be attributed to their role as
Scribble module protein interactors
In addition to their roles in cell polarity, the Scribble module proteins interact with many proteins involved in different cellular processes, such as cell adhesion, membrane trafficking, cell migration and cellular signaling (see Fig. 1, Fig. 2, Fig. 3, Table 1, Table 2, Table 3). Despite their common role in regulating cell polarity, Scrib, Dlg and Lgl interact with mostly distinct protein interactors. We will highlight below some examples of interacting proteins and the motifs within the
Scribble module proteins in the regulation of cell signaling pathways
Since Scrib and Dlg are similar in structure and function, whilst Lgl is structurally and functionally different, with its function tightly linked to aPKC and the Par complex function, we will consider Scrib and Dlg separately to Lgl and aPKC/Par in discussing their regulation of cell signaling pathways.
Conclusions and Perspectives
We have highlighted in this review, the myriad of Scribble module interacting proteins and how they are involved in cell signaling pathways. It is clear that there is considerably complexity in the protein interactions that have been documented to occur with Scribble module proteins and in the regulation of signaling pathways. Although Scrib, Dlg and Lgl play a common function in cell polarity regulation, they interact with distinct proteins in the regulation of various signaling pathways, and
Acknowledgements
This work was supported by an National Health and Medical Research Council Australia (NHMRC) Project Grant (APP1103871) to MK, POH and HER, an NHMRC Fellowship (APP1020056) to PH, an Australian Research Council Fellowship (FT130101349) to MK, a Juan de la Cierva-Incorporacion postdoctoral fellowship (IJCI-2014-19272) from the Spanish Ministerio de Ciencia e Innovacion (MICINN) to MP, a Australian Government RTP Scholarship to RS, and funds from La Trobe University and the La Trobe Institute of
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