Cell junction organization pathway

General description
cell-cell junction organization can be categorized into adherens and tight junction interactions. These interactions connect neighbouring cells and links intracellularly to the actin cytoskeleton and signalling pathways. Tight junction is composed of transmembrane proteins, holding adjacent cells in close contact, controlling paracellular permeability thus forming barrier. Tight junction is typical of epithelial cells, but can be formed by endothelial cells as well. Adherens junction is multi-protein complexes that promotes homotypic cell adhesion in almost all types of tissues. Adherens junction also binds directly to cytoplasmic proteins, which regulate the organization of cytoskeleton, and signalling events. Adherens junction also regulates cell polarity and shape (Hartsock & Nelson, 2008)⁠.
  • Hartsock, A., & Nelson, W. J. (2008). Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton. Biochimica et Biophysica Acta - Biomembranes. doi:10.1016/j.bbamem.2007.07.012
Reactome REACT_20676.1
KEGG Pathways
Involvement in Alzheimer's disease

It has been proposed that inflammation and blood-brain barrier dysfunction are crucial in AD pathogenesis (Stolp & Dziegielewska, 2009; Ujiie, Dickstein, Carlow, & Jefferies, 2003)⁠. The abnormalities of endothelial tight junction has been observed in brain biopsies from AD patients (Stewart & Hayakawa, 1992)⁠. It seems that Abeta 1-42 can cause relocation and affect expression of tight junction proteins (Marco & Skaper, 2006), thus disrupting the integrity of blood-brain barrier.

There are very few studies on involvement of adherens junction in AD. Two genes, PVRL2 and FERMT2, showed significant variation in GWAS studies, are both involved in adherens junction organization pathway(Harold et al., 2009; Lambert et al., 2013)⁠.

  • Marco, S., & Skaper, S. D. (2006). Amyloid beta-peptide1-42 alters tight junction protein distribution and expression in brain microvessel endothelial cells. Neuroscience Letters, 401, 219–224. doi:10.1016/j.neulet.2006.03.047
  • Stewart, P., & Hayakawa, K. (1992). A morphometric study of the blood-brain barrier in Alzheimer’s disease. Laboratory Investigation; a Journal of Technical Methods and Pathology, 67, 734–742. Retrieved from http://apps.isiknowledge.com/full_record.do?product=WOS&search_mode=Refi...@77dpaPIFo4kD&page=15&doc=743\nhttp://www.ncbi.nlm.nih.gov/pubmed/1460864
  • Stolp, H. B., & Dziegielewska, K. M. (2009). Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathology and Applied Neurobiology, 35, 132–146. doi:10.1111/j.1365-2990.2008.01005.x
  • Ujiie, M., Dickstein, D. L., Carlow, D. A., & Jefferies, W. A. (2003). Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model. Microcirculation (New York, N.Y. : 1994), 10, 463–470. doi:10.1038/sj.mn.7800212
  • Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., … Williams, J. (2009). Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet, 41(10), 1088–1093. doi:10.1038/ng.440
  • Lambert, J.-C., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., … Amouyel, P. (2013). Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet, 45(12), 1452–1458. doi:10.1038/ng.2802
Proteins involved