THE SUBCELLULAR-DISTRIBUTION OF EARLY ENDOSOMES IS AFFECTED BY THE ANNEXIN-II(2)P11(2) COMPLEX

The tyrosine kinase substrate annexin II is a member of a multigene fa mily of Ca2+ and lipid-binding proteins which have been implicated in a number of membrane-related events. We have analyzed the subcellular distribution of annexin II in relation to other cellular components in normal and specifically manipulated MDCK cells. In a polarized monola yer of MDCK cells annexin II and its cellular ligand p11 are restricte d almost exclusively to the cortical regions of the cells which also c ontain peripheral early endosomes. Treatment of the polarized cells wi th low Ca2+ medium leads to a disintegration of the cortical cytoskele ton and a translocation of both, the annexin II2p11(2) complex and ear ly endosomes, to the cytoplasm. A similar translocation which is howev er specific for the annexin II2p11(2) complex and early endosomes and does not affect other elements of the cell cortex is observed in cells expressing a trans-dominant annexin II-p11 mutant. This chimeric muta nt protein causes the aggregation of endogenous annexin II and p11 and the simultaneous detachment of early endosomes from the cell peripher y resulting in the binding of the early endosomes but no other compone nts of the endocytotic or biosynthetic pathways to the annexin II/p11 aggregates. The specificity of this effect argues for the association of the annexin II2P11(2) complex with early endosomes and suggests tha t this association contributes to establish the peripheral localizatio n of early endosomal structures.