DIFFERENTIAL ORGANIZATION OF DESMIN AND VIMENTIN IN MUSCLE IS DUE TO DIFFERENCES IN THEIR HEAD DOMAINS

In most myogenic systems, synthesis of the intermediate filament (IF) protein vimentin precedes the synthesis of the muscle-specific IF prot ein desmin. In the dorsal myotome of the Xenopus embryo, however, ther e is no preexisting vimentin filament system and desmin's initial orga nization is quite different from that seen in vimentin-containing myoc ytes (Cary and Klymkowsky, 1994. Differentiation. In press.). To deter mine whether the organization of Ifs in the Xenopus myotome reflects f eatures unique to Xenopus or is due to specific properties of desmin, we used the injection of plasmid DNA to drive the synthesis of vimenti n or desmin in myotomal cells. At low levels of accumulation, exogenou s vimentin and desmin both enter into the endogenous desmin system of the myotomal cell. At higher levels exogenous vimentin forms longitudi nal IF systems similar to those seen in vimentin-expressing myogenic s ystems and massive IF bundles. Exogenous desmin, on the other hand, fo rmed a reticular IF meshwork and non-filamentous aggregates. In embryo nic epithelial cells, both vimentin and desmin formed extended IF netw orks. Vimentin and desmin differ most dramatically in their NH2-termin al ''head'' regions. To determine whether the head region was responsi ble for the differences in the behavior of these two proteins, we cons tructed plasmids encoding chimeric proteins in which the head of one w as attached to the body of the other. In muscle, the vimentin head-des min body (VDD) polypeptide formed longitudinal Ifs and massive IF bund les like vimentin. The desmin head-vimentin body (DVV) polypeptide, on the other hand, formed IF meshworks and non-filamentous structures li ke desmin. In embryonic epithelial cells DVV formed a discrete filamen t network while VDD did not. Based on the behavior of these chimeric p roteins, we conclude that the head domains of vimentin and desmin are structurally distinct and not interchangeable, and that the head domai n of desmin is largely responsible for desmin's muscle-specific behavi ors.