The skin water barrier, essential for terrestrial life, is formed by a multilayered stratifying epithelium, which shows a polarized distribution of both differentiation and intercellular junction markers. Recently, several reports showed the crucial importance of tight junctions for the in vivo water barrier function of the skin. In simple epithelial cells, intercellular junction formation is closely coupled to the establishment of polarity. However, if and how polarity proteins contribute to epidermal differentiation and junction formation is not yet known. Here, we have characterized the localization and isoform expression of the polarity protein atypical PKC (aPKC) and its binding partners Par3 and Par6 in epidermis and primary keratinocytes of mice. Their distribution is only partially overlapping in the granular layer, the site of functional tight junctions, suggesting that next to a common Par3/Par6/aPKC function they also may have functions independent of each other. Both aPKCzeta and aPKCiota/lambda, are expressed in the epidermis but only aPKCiota/lambda showed a strong enrichment in the junctions, suggesting that this aPKC isoform is important for epidermal tight junction function. Indeed, inhibition of aPKC function showed that endogenous aPKC is crucial for in vitro barrier function and this required the presence of both the Par3 and Par6 binding sites.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/sj.jid.5700621 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A PDZ-kinase allosteric relay mediates Par complex regulator exchange.
J Biol Chem
December 2024
Department of Chemistry and Biochemistry, Institute of Molecular Biology, 1229 University of Oregon, Eugene, Oregon, USA. Electronic address:
The Par complex polarizes the plasma membrane of diverse animal cells using the catalytic activity of atypical PKC (aPKC) to pattern substrates. Two upstream regulators of the Par complex, Cdc42 and Par-3, bind separately to the complex to influence its activity in different ways. Each regulator binds a distinct member of the complex, Cdc42 to Par-6 and Par-3 to aPKC, making it unclear how they influence one another's binding.
View Article and Find Full Text PDFaPKC/Par3/Par6 polarity complexes regulate podocyte motility and crescent formation in the progression of ANCA-associated vasculitis.
Rheumatology (Oxford)
December 2024
Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
Objectives: Podocyte bridging may be a key initial event occurring early in crescent formation. This study aims to probe the underlying mechanism of atypical protein kinase C (aPKC)/protease-activated receptor 3(Par3)/Par6 polarity complexes on podocyte motility and crescent formation during the progression of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
Methods: The effects of anti-TNF-α monoclonal antibody (mAb) on the crescent formation, localization and expression of aPKC/Par3/Par6 polarity complexes, and activities of small GTPases (Rho/Rac1/Cdc42) were explored in an AAV mouse model.
Cell polarity proteins promote macropinocytosis in response to metabolic stress.
Nat Commun
December 2024
Cancer Metabolism and Microenvironment Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Article Synopsis
- Macropinocytosis is a survival strategy used by cancer cells, especially in nutrient-poor environments, relying heavily on glutamine to sustain themselves, particularly in pancreatic ductal adenocarcinoma (PDAC) cells.
- The atypical protein kinase C (aPKC) enzymes, specifically PKCζ and PKCι, play a crucial role in regulating macropinocytosis by interacting with scaffold proteins that influence cell structure and function.
- The research shows that aPKCs enhance macropinocytosis through the relocation of Par3 to microtubules, and their depletion adversely affects cell viability, which can be reversed by restoring macropinocytosis, highlighting the significance of aPKCs in supporting
A PDZ-kinase allosteric relay mediates Par complex regulator exchange.
bioRxiv
October 2024
Institute of Molecular Biology, Department of Chemistry and Biochemistry, 1229 University of Oregon, Eugene, OR 97403.
The Par complex polarizes the plasma membrane of diverse animal cells using the catalytic activity of atypical Protein Kinase C (aPKC) to pattern substrates. Two upstream regulators of the Par complex, Cdc42 and Par-3, bind separately to the complex to influence its activity in different ways. Each regulator binds a distinct member of the complex, Cdc42 to Par-6 and Par-3 to aPKC, making it unclear how they influence one another's binding.
View Article and Find Full Text PDFOligomerization and positive feedback on membrane recruitment encode dynamically stable PAR-3 asymmetries in the zygote.
bioRxiv
August 2024
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637.
Studies of PAR polarity have emphasized a paradigm in which mutually antagonistic PAR proteins form complementary polar domains in response to transient cues. A growing body of work suggests that the oligomeric scaffold PAR-3 can form unipolar asymmetries without mutual antagonism, but how it does so is largely unknown. Here we combine single molecule analysis and modeling to show how the interplay of two positive feedback loops promote dynamically stable unipolar PAR-3 asymmetries in early embryos.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!