The tumor suppressor protein TSLC1 is involved in cell-cell adhesion.
TSLC1 is a tumor suppressor gene encoding a member of the immunoglobulin (Ig) superfamily. The significant homology of its extracellular domain with those of other Ig superfamily cell adhesion molecules (IgCAMs) has raised the possibility that TSLC1 participates in cell-cell interactions. In this study, the physiological properties of TSLC1 were investigated in Madin-Darby canine kidney (MDCK) cells expressing TSLC1 tagged with green fluorescent protein (GFP) as well as in the cells that express endogenous TSLC1. Biochemical analysis has revealed that TSLC1 is an N-linked glycoprotein with a molecular mass of 75 kDa and that it forms homodimers through cis interaction within the plane of the cell membranes. Confocal laser scanning microcopy of the cells expressing TSLC1 showed the localization patterns characteristic to adhesion molecules. At the beginning of cell attachment, TSLC1 accumulated in interdigitated structures at cell-cell boundaries, but, when cells reached a confluence, TSLC1 was distributed all along the cell membranes. In polarized cells, TSLC1 was recruited to the lateral membrane, implying trans interaction of TSLC1 between neighboring cells. In support of this notion, MDCK cells expressing TSLC1-GFP showed a significant level of cell aggregation in the absence or presence of Ca(2+) and Mg(2+). Taken together, these results indicate that TSLC1 mediates intracellular adhesion through homophilic interactions in a Ca(2+)/Mg(2+)-independent manner.
Masuda
Mari
M
Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institutes, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Yageta
Mika
M
Fukuhara
Hiroshi
H
Kuramochi
Masami
M
Maruyama
Tomoko
T
Nomoto
Akio
A
Murakami
Yoshinori
Y
D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D002449:Cell Aggregation; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D019281:Dimerization; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins; D008274:Magnesium / Q000502:physiology; D008565:Membrane Proteins; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D025521:Tumor Suppressor Proteins
C403514:CADM1 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D008274:Magnesium; D002118:Calcium