Clustering and Negative Feedback by Endocytosis in Planar Cell Polarity Signaling Is Modulated by Ubiquitinylation of Prickle


Many epithelial cells display a level of organization in which cellular structures or appendages are positioned asymmetrically within the cell along an axis perpendicular to the apical-basal axis of the cell. When the direction of this polarization is coordinated within the plane of the epithelium, this phenomenon is referred to as planar cell polarity (PCP). PCP is organized, at least in part, by a group of molecules that interact across cell-cell junctions and segregate into two groups that localize on opposite sides of each cell. Their asymmetric localization is thought to both produce molecular asymmetry, and to mark polarized domains within the cell for subsequent morphological polarization. In segregating to produce molecular asymmetry, these proteins participate in both positive and negative feedback, much like ferromagnets, to align their localization within and between neighboring cells. In this work, we identify a mechanism for negative feedback that utilizes the protein Prickle, one of the PCP signaling components. Levels of Prickle are precisely regulated, in part by a ubiquitinylation mechanism that targets excess protein for degradation. Prickle mediates internalization and removal of one class of PCP proteins, thereby causing repulsion of opposite ‘poles.’ Excess Prickle disrupts this mechanism and interferes with establishing polarity.


Vyšlo v časopise: Clustering and Negative Feedback by Endocytosis in Planar Cell Polarity Signaling Is Modulated by Ubiquitinylation of Prickle. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005259
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005259

Souhrn

Many epithelial cells display a level of organization in which cellular structures or appendages are positioned asymmetrically within the cell along an axis perpendicular to the apical-basal axis of the cell. When the direction of this polarization is coordinated within the plane of the epithelium, this phenomenon is referred to as planar cell polarity (PCP). PCP is organized, at least in part, by a group of molecules that interact across cell-cell junctions and segregate into two groups that localize on opposite sides of each cell. Their asymmetric localization is thought to both produce molecular asymmetry, and to mark polarized domains within the cell for subsequent morphological polarization. In segregating to produce molecular asymmetry, these proteins participate in both positive and negative feedback, much like ferromagnets, to align their localization within and between neighboring cells. In this work, we identify a mechanism for negative feedback that utilizes the protein Prickle, one of the PCP signaling components. Levels of Prickle are precisely regulated, in part by a ubiquitinylation mechanism that targets excess protein for degradation. Prickle mediates internalization and removal of one class of PCP proteins, thereby causing repulsion of opposite ‘poles.’ Excess Prickle disrupts this mechanism and interferes with establishing polarity.


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