CELL-SURFACE EXPRESSION OF RECEPTORPROTEIN TYROSINE PHOSPHATASE RPTP-MU IS REGULATED BY CELL-CELL CONTACT

RPTP mu is a transmembrane protein tyrosine phosphatase with an adhesi on molecule-like ectodomain. It has recently been shown that RPTP mu m ediates hemophilic interactions when expressed in insect cells. In thi s study, we have examined how RPTP mu may function as a cell contact r eceptor in mink lung epithelial cells, which express RPTP mu endogenou sly, as well as in transfected 3T3 cells. We find that RPTP mu has a r elatively 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 expon entially growing cells. Immunofluorescence analysis reveals that surfa ce expression of RPTP mu is restricted to regions of tight cell-cell c ontact. RPTP mu surface expression increases significantly with increa sing cell density, This density-induced upregulation of RPTP mu is ind ependent of its catalytic activity and is also observed when transcrip tion is driven by a constitutive promoter, indicating that modulation of RPTP mu surface expression occurs posttranscriptionally. Based on o ur results, we propose the following model of RPTP mu function: In the absence of cell-cell contact, newly synthesized RPTP mu molecules are rapidly cleared from the cell surface. Cell-cell contact causes RPTP mu, to be trapped at the surface through homophilic binding, resulting in accumulation of RPTP mu at intercellular contact regions. This con tact-induced clustering of RPTP mu. may then lead to tyrosine dephosph orylation of intracellular substrates at cell-cell contacts.