scholarly journals The positioning and segregation of apical cues during epithelial polarity establishment in Drosophila

2005 ◽  
Vol 170 (5) ◽  
pp. 813-823 ◽  
Author(s):  
Tony J.C. Harris ◽  
Mark Peifer
Keyword(s):  
Protein Kinase C ◽  
Cell Polarity ◽  
Structure And Function ◽  
Epithelial Polarity ◽  
Kinase C ◽  
Binding Partners ◽  
Apical Domain ◽  
Epithelial Structure ◽  
And Function ◽  
Key Steps

Cell polarity is critical for epithelial structure and function. Adherens junctions (AJs) often direct this polarity, but we previously found that Bazooka (Baz) acts upstream of AJs as epithelial polarity is first established in Drosophila. This prompted us to ask how Baz is positioned and how downstream polarity is elaborated. Surprisingly, we found that Baz localizes to an apical domain below its typical binding partners atypical protein kinase C (aPKC) and partitioning defective (PAR)-6 as the Drosophila epithelium first forms. In fact, Baz positioning is independent of aPKC and PAR-6 relying instead on cytoskeletal cues, including an apical scaffold and dynein-mediated basal-to-apical transport. AJ assembly is closely coupled to Baz positioning, whereas aPKC and PAR-6 are positioned separately. This forms a stratified apical domain with Baz and AJs localizing basal to aPKC and PAR-6, and we identify specific mechanisms that keep these proteins apart. These results reveal key steps in the assembly of the apical domain in Drosophila.

scholarly journals Distinct activities of Scrib module proteins organize epithelial polarity

2020 ◽  
Vol 117 (21) ◽  
pp. 11531-11540 ◽  
Author(s):  
Mark J. Khoury ◽  
David Bilder
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Epithelial Polarity ◽  
Protein Protein Interactions ◽  
Kinase C ◽  
Mutual Antagonism ◽  
Discs Large ◽  
Lethal Giant Larvae ◽  
Epithelial Structure ◽  
And Function

A polarized architecture is central to both epithelial structure and function. In many cells, polarity involves mutual antagonism between the Par complex and the Scribble (Scrib) module. While molecular mechanisms underlying Par-mediated apical determination are well-understood, how Scrib module proteins specify the basolateral domain remains unknown. Here, we demonstrate dependent and independent activities of Scrib, Discs-large (Dlg), and Lethal giant larvae (Lgl) using theDrosophilafollicle epithelium. Our data support a linear hierarchy for localization, but rule out previously proposed protein–protein interactions as essential for polarization. Cortical recruitment of Scrib does not require palmitoylation or polar phospholipid binding but instead an independent cortically stabilizing activity of Dlg. Scrib and Dlg do not directly antagonize atypical protein kinase C (aPKC), but may instead restrict aPKC localization by enabling the aPKC-inhibiting activity of Lgl. Importantly, while Scrib, Dlg, and Lgl are each required, all three together are not sufficient to antagonize the Par complex. Our data demonstrate previously unappreciated diversity of function within the Scrib module and begin to define the elusive molecular functions of Scrib and Dlg.

scholarly journals The structure and function of protein kinase C-related kinases (PRKs)

2021 ◽  
Author(s):  
Georgios Sophocleous ◽  
Darerca Owen ◽  
Helen R. Mott
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Interactions ◽  
Bacterial Infections ◽  
Lipid Binding ◽  
Structure And Function ◽  
Structural Description ◽  
Kinase C ◽  
Molecular Events ◽  
And Function

The protein kinase C-related kinase (PRK) family of serine/threonine kinases, PRK1, PRK2 and PRK3, are effectors for the Rho family small G proteins. An array of studies have linked these kinases to multiple signalling pathways and physiological roles, but while PRK1 is relatively well-characterized, the entire PRK family remains understudied. Here, we provide a holistic overview of the structure and function of PRKs and describe the molecular events that govern activation and autoregulation of catalytic activity, including phosphorylation, protein interactions and lipid binding. We begin with a structural description of the regulatory and catalytic domains, which facilitates the understanding of their regulation in molecular detail. We then examine their diverse physiological roles in cytoskeletal reorganization, cell adhesion, chromatin remodelling, androgen receptor signalling, cell cycle regulation, the immune response, glucose metabolism and development, highlighting isoform redundancy but also isoform specificity. Finally, we consider the involvement of PRKs in pathologies, including cancer, heart disease and bacterial infections. The abundance of PRK-driven pathologies suggests that these enzymes will be good therapeutic targets and we briefly report some of the progress to date.

scholarly journals Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

Oncotarget ◽  
2016 ◽  
Vol 7 (8) ◽  
pp. 8532-8545 ◽  
Author(s):  
Ahmed S. Ibrahim ◽  
Suchreet Mander ◽  
Khaled A. Hussein ◽  
Nehal M. Elsherbiny ◽  
Sylvia B. Smith ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Structure And Function ◽  
Age Related Macular Degeneration ◽  
Pigment Epithelial ◽  
Age Related ◽  
Epithelial Structure ◽  
And Function
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