This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.E-cadherin is a 120-kDa membrane glycoprotein, expressed in epithelial cells, which is the main player in establishing adherens junctions between cells. The adherens junctions have both intra and extracellular anchorage points in order to regulate cell-cell interactions.[1-2] Alterations in the assembly or disassembly of adherens junctions occur in association with major changes in the state of cell, including differentiation and proliferation [3], as well as in cancer progression. Loss of E-cadherin function is a frequent event in many types of cancer, commonly caused by diminished or aberrant E-cadherin expression. [4] Recent studies have indicated that the N-glycosylation pattern of E-cadherin has a role in the molecular organization of adherens junctions. Specifically, the presence of complex N-glycans is associated with destabilized adherens junctions. [5] Investigation into the structural characteristics of E-cadherin, specifically its N-glycosylation pattern and protein binding partners, provide insight into E-cadherin mediated adhesion and cell signaling functions.Isolation of this large membrane protein has required the development of specific methods. Our methodology has isolated pools of E-cadherin with different binding partners and different N-glycosylation states, depending on cell status. The forms of E-cadherin in malignant cells are more highly glycosylated than are those in non-malignant cells; they migrate at a higher apparent weight, as detected by Western blot and peptide mass fingerprinting of excised SDS-PAGE bands. Through continued studies to identify the protein components, we have found that E-cadherin is associated with destabilizing proteins in malignant cells to a greater extent than when it is present in non-malignant cells. E-cadherin N-glycosylation has also been investigated, specifically site occupancy and N-glycan composition. MALDI-TOF MS analysis of in-gel enzymatically released N-glycans suggests E-cadherin contains predominantly complex N-glycans. This work highlights that cell context, the recruitment of specific proteins to the adhesion complex, along with specific structural modifications to E-cadherin may define the overall stability of E-cadherin mediated adhesion.References:1. Gottardi CJ, Wong E, Gumbiner BM. J Cell Biol 2001; 153(5): 1049-602. Perez-Moreno M, Jamora C, Fuchs E. Cell 2003; 112(4): 535-483. Gumbiner BM. Nat Rev Mol Cell Biol 2005; 6:622-6344. Wheelock MJ, Johnson KR. Annu Rev Cell Dev Biol 2003; 19:207-355. Liwosz A, Lei T, and Kukuruzinska MA. J Biol Chem 2006; 281:23138-49.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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