Special typeofmorphological reorganization induced byphorbol ester: Reversible partition ofcell intomotile andstable domains

Thephorbol ester phorbol 12-myristate 13- acetate (PMA)induced reversible alteration oftheshape of fibroblastic cells ofcertain transformed lines-namely, parti- tion ofthecells into twotypes ofdomains: motile bodyactively extending large lamellas andstable narrowcytoplasmic pro- cesses. Dynamic observations haveshownthat stable processes areformed frompartially retracted lamellas andfromcon- tracted tail parts ofcell bodies. Immunofluorescence micros- copyandelectron microscopy ofplatinum replicas ofcytoskel- etonhaveshownthat PMA-induced narrow processes arerich inmicrotubules andintermediate filaments butrelatively poor inactin microfilaments; incontrast, lamellas andcell bodies contained numerous microfilaments. Colcemid-induced depo- lymerization ofmicrotubules ledtocontraction ofPMA- induced processes; cytochalasin Bprevented this contraction. Itissuggested that PMA-induced separation ofcell into motile andstable parts isduetodirectional movement ofactin structures along themicrotubular framework. Similar move- mentsmayplayanimportant role invarious normal morpho- genetic processes. Reversible morphological reorganizations offibroblasts and other cultured cells areactively studied asprototypes of normal morphogenetic processes; alterations ofcytoskeleton regulated bythemembrane-generated signals seemtoplay central roles inthese reorganizations (for reviews, seerefs. 1-3). Inthis paperwedescribe aspecial typeofreversible alteration ofcell shape andcytoskeleton induced incertain fibroblastic lines bythetumorpromoter phorbol 12-myristate 13-acetate (PMA). Thisagent caused reversible cell partition into amotile pseudopod-forming bodyandnonmotile elon- gated processes rich inmicrotubules andintermediate fila- ments.Analysis ofthis reorganization suggests thatalter- ations ofinteractions between theactin cortex andmicrotu- bules areofkeyimportance inits development. Itispossible that reorganizations ofasimilar typeareinvolved innormal morphogenetic processes-e.g., intheformation ofneurites byneural cells, inforward translocation ofpolarized fibro- blasts, etc.