Interaction between band 3 and ankyrin begins in early compartments of the secretory pathway and is essential for band 3 processing.

In many cell types, membrane proteins are specifically segregated to particular areas of the cell surface. It is known that this segregation is stabilized by anchorage proteins which interact with the cytoskeleton. However, the mechanism by which the interactions with anchorage proteins occur, as well as whether they may also play a role in the process of sorting, is not known. Using differentiated murine erythroleukemic cells, we have investigated the association between band 3 (a major transmembrane anion exchanger), and ankyrin (a cytoplasmic protein that links band 3 to the cytoskeleton). Our data demonstrate that the association between band 3 and ankyrin occurs in the endoplasmic reticulum or the first Golgi compartment. These data support a model in which the band 3-ankyrin complex is inserted as a "cassette" at the plasma membrane into the cytoskeletal network. Biosynthetic studies on cotransfected 293 cells with cDNAs encoding band 3 and the band 3 binding fragment of ankyrin (AnK-90), suggest that ankyrin is not only responsible for the anchorage of band 3 to the cytoskeleton but is also involved in the exit of band 3 out of the endoplasmic reticulum.