Cell surface expression of receptor protein tyrosine phosphatase RPTPμ is regulated by cell-cell contact

RPTPμ is a transmembrane protein tyrosine phosphatase with an adhesion molecule-like ectodomain. It has recently been shown that RPTPμ mediates homophilic interactions when expressed in insect cells. In this study, we have examined how RPTPμ may function as a cell contact receptor in mink lung epithelial cells, which express RPTPμ endogenously, as well as in transfected 3T3 cells. We find that RPTPμ has a relatively short half-life (3-4 hours) and undergoes posttranslational cleavage into two noncovalently associated subunits, with both cleaved and uncleaved molecules being present on the cell surface (roughly at a 1:1 ratio); shedding of the ectodomain subunit is observed in exponentially growing cells. Immunofluorescence analysis reveals that surface expression of RPTPμ is restricted to regions of tight cell-cell contact. RPTPμ surface expression increases significantly with increasing cell density. This density-induced upregulation of RPTPμ is independent of its catalytic activity and is also observed when transcription is driven by a constitutive promoter, indicating that modulation of RPTPμ surface expression occurs posttranscriptionally. Based on our results, we propose the following model of RPTPμ function: In the absence of cell-cell contact, newly synthesized RPTPμ molecules are rapidly cleared from the cell surface. Cell-cell contact causes RPTPμ, to be trapped at the surface through homophilic binding, resulting in accumulation of RPTPμ at intercellular contact regions. This contact-induced clustering of RPTPμ may then lead to tyrosine dephosphorylation of intracellular substrates at cell- cell contacts.