Connexins and Cadherin Cross-talk in the Pathogenesis of Prostate Cancer
Abstract
Gap junctions are ensembles of cell-cell channels that are formed by proteins called connexins. They permit the passage of small molecules between cells and maintain homeostasis. We have found that connexin32 and connexin43 are assembled into gap junctions in normal prostate but remain intracellular in prostate tumors. Our studies showed that the expression of anti-metastatic E-cadherin facilitated gap junction assembly whereas the expression of pro-invasive N-cadherin disrupted assembly. We hypothesized that gap junction assembly was the downstream target of signaling initiated by cadherins. We had proposed 2 specific aims to test this hypothesis. The proposed studies of Aim 1 were to determine how E-cadherin mediated cell-cell adhesion controlled gap junction assembly in prostate cancer cells whereas of aim 2 were to determine the molecular mechanisms by which E-cadherin and N-cadherin modulate gap junction assembly differentially. We have identified key motifs that regulate the endocytosis of connexin43 and connexin32 by clathrin-mediated pathway. Endocytosis of connexin43 is regulated through phosphorylation of serine 279 and 282 via clathrin-mediated pathway whereas that of connexin32 is regulated by three dileucinelike motifs in its cytoplasmic tail. Expression of mutant connexin32, in which the two dileucine-like motifs are mutated, results in the formation of large gap junctions. Finally, we have identified a new post-translational modification of 120-catenin that affects cadherin-connexin cross talk.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA602333
Entities
People
- Keith R. Johnson
- Parmender P Mehta
Organizations
- University of Nebraska Medical Center