Nuclear Signaling from Cadherin Adhesion Complexes

Abstract

The arrival of multicellularity in evolution facilitated cell–cell signaling in conjunction with adhesion. As the ectodomains of cadherins interact with each other directly in trans (as well as in cis), spanning the plasma membrane and associating with multiple other entities, cadherins enable the transduction of “outside-in” or “inside-out” signals. We focus this review on signals that originate from the larger family of cadherins that are inwardly directed to the nucleus, and thus have roles in gene control or nuclear structure–function. The nature of cadherin complexes varies considerably depending on the type of cadherin and its context, and we will address some of these variables for classical cadherins versus other family members. Substantial but still fragmentary progress has been made in understanding the signaling mediators used by varied cadherin complexes to coordinate the state of cell–cell adhesion with gene expression. Evidence that cadherin intracellular binding partners also localize to the nucleus is a major point of interest. In some models, catenins show reduced binding to cadherin cytoplasmic tails favoring their engagement in gene control. When bound, cadherins may serve as stoichiometric competitors of nuclear signals. Cadherins also directly or indirectly affect numerous signaling pathways (e.g., Wnt, receptor tyrosine kinase, Hippo, NFκB, and JAK/STAT), enabling cell–cell contacts to touch upon multiple biological outcomes in embryonic development and tissue homeostasis.

Maternal separation induces hippocampal changes in cadherin-1 (CDH-1) mRNA and recognition memory impairment in adolescent mice

“…In addition, CDH adhesion molecules are grouped into type I and type II subfamily, playing an substantial role in the regulation of synaptic plasticity and MATERNAL SEPARATION, RECOGNITION MEMORY AND CADHERIN mRNA 6 specificity (Basu, Taylor, & Williams, 2015;Gärtner, Fornasiero, & Dotti, 2015;Seong, Yuan, & Arikkath, 2015;Takeichi, 2007). -Catenin (-Cat) is a cell adhesion molecule associated with the cytoplasmic domain of CDH and directly linked to the acting-binding proteins in synaptic junctions (McCrea, Maher, & Gottardi, 2015), regulating the synaptic connectivity and activity (Salinas & Price, 2005;Seong et al, 2015). In addition to the role of -Cat in CDH-mediated cell adhesion, it also plays a critical role in the canonical Wnt signal transduction pathway, and the Wnt/-Cat complex is involved in modulating synaptic plasticity that is underlying long-term memory (Chen, Park, & Tang, 2006;Maguschak & Ressler, 2008.…”

Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis

“…Based on the results described above, the adhesive and transcriptional "pools" of b-catenin in dermomyotomal muscle progenitor cells might be viewed as distinct; that is, they are involved in either cell -cell adhesion or Wnt signal-dependent activation of Myf5 expression, but not both. However, nuclear b-catenin signaling from adhesion complexes can occur (McCrea et al 2015), and recent results from the Marcelle group suggest that this process may be involved in commitment of dermomyotomal progenitor cells to the muscle lineage. These investigators have studied the role of neural crest cells in promoting somitic myogenesis.…”

Nuclear α-catenin mediates the DNA damage response via β-catenin and nuclear actin

“…WNT stimulation promotes β-catenin translocation into the nucleus, where β-catenin interacts with transcription factors and chromatin remodelers (Valenta et al, 2012). Another population of β-catenin is found at cell-cell adherens junctions; here, β-catenin binds cadherin proteins along with the F-actin-binding protein α-catenin, bridging the cytoskeleton and cellular junctions (McCrea et al, 2015;Valenta et al, 2012). This junctional population of β-catenin may also be responsive to WNT signaling (Hendriksen et al, 2008), suggesting that crosstalk between WNT signaling and adhesion complexes can be mediated by β-catenin (McCrea et al, 2015).…”

“…Another population of β-catenin is found at cell-cell adherens junctions; here, β-catenin binds cadherin proteins along with the F-actin-binding protein α-catenin, bridging the cytoskeleton and cellular junctions (McCrea et al, 2015;Valenta et al, 2012). This junctional population of β-catenin may also be responsive to WNT signaling (Hendriksen et al, 2008), suggesting that crosstalk between WNT signaling and adhesion complexes can be mediated by β-catenin (McCrea et al, 2015). Inactivating mutations in α-catenin, activating mutations in β-catenin and changes in the expression levels of these proteins have been repeatedly tied to various cancers (Aaltomaa et al, 1999;Anttila et al, 1998;Gofuku et al, 1999;Lifschitz-Mercer et al, 2001;Matsui et al, 1994;Nakopoulou et al, 2002;Richmond et al, 1997;Rimm et al, 1995;Shiozaki et al, 1994;Silvis et al, 2011;Tanaka et al, 2003;van Oort et al, 2007).…”