Schematic involvement of small GTPases in Cx43 transport. Left panel Distribution and effects of three small GTPases that act in the biosynthetic pathway, Sar1, Arf1, and Arf6, on the transport of Cx43. Differential blocks induced by GDP- and GTP-restricted Sar1 on ER-to-Golgi transport of Cx43: Sar1T39N prevents assembly into ER exit sites—left, Sar1H79G blocks Cx43 in ER exit sites—right (monomeric and oligomeric forms of Cx43 are depicted in red). Cx43 exit from the Golgi is blocked by ARF1Q71L. Recycling and removal of Cx43 at the PM is Arf6-dependent. This step may be important for regulation of Cx43 at the PM in response to extracellular signals, migration, or initiation of transformation. Middle panel ER-Golgi-PM transport of connexins and formation of gap junctions at the cell–cell interface upon contact. Right panel Possible role of 14-3-3 proteins in Cx43 oligomerization/segregation into ERES