Protocadherin of the liver, kidney, and colon associates with detergent-resistant membranes during cellular differentiation.
Protocadherin LKC (PLKC) is a member of the heterogeneous subgroup of protocadherins that was identified and described as a potential tumor-suppressor gene involved in contact inhibition (Okazaki, N., Takahashi, N., Kojima, S., Masuho, Y., and Koga, H. (2002) Carcinogenesis 23, 1139-1148 and Ose, R., Yanagawa, T., Ikeda, S., Ohara, O., and Koga, H. (2009) Mol. Oncol. 3, 54-66). Several aspects of the structure, posttranslational processing, targeting, and function of this new protocadherin are still not known. Here, we demonstrate that the expression of PLKC at the apical membrane domain and its concentration at regions of cell-cell contacts occur concomitantly with significant elevation of PLKC-mRNA levels. Furthermore, it can be found within the adherens junctions, but it does not colocalize with tight junctions proteins ZO-1 and occludin, respectively. Additionally, unlike E-cadherin, PLKC is not redistributed upon Ca(2+) removal. Biosynthetic labeling revealed N- and O-glycosylation as posttranslational modifications as well as a fast transport to the cell surface and a low turnover rate. During differentiation, PLKC associates with detergent-resistant membranes that trigger its redistribution from intracellular membranes to the cell surface. This association occurs concomitant with alterations in the glycosylation pattern. We propose a role for PLKC in the establishment of a proper epithelial cell polarity that requires O-linked glycosylation and association of the protein with detergent-resistant membranes.
Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover D-30559, Germany.
Michael P
MP
Krahn
Sandra
S
Rizk
Marwan
M
Alfalah
Marc
M
Behrendt
Hassan Y
HY
Naim
D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003902:Detergents / Q000494:pharmacology; D004285:Dogs; D006031:Glycosylation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D015820:Cadherins; D003902:Detergents; D008565:Membrane Proteins; D062793:Occludin; D010750:Phosphoproteins; D012333:RNA, Messenger; D062826:Zonula Occludens-1 Protein; D002118:Calcium