Evidence for the involvement of annexin 6 in the trafficking between the endocytic compartment and lysosomes

Annexins are a family of calcium-dependent phospholipid-binding proteins, w hich have been implicated in a variety of biological processes including me mbrane trafficking. The annexin 6/lgp120 prelysosomal compartment of NRK ce lls was loaded with low-density lipoprotein (LDL) and then its transport fr om this endocytic compartment and its degradation in lysosomes were studied . NRK cells were microinjected with the mutated annexin 6 (anx6(1-175)), to assess the possible involvement of annexin 6 in the transport of LDL from the prelysosomal compartment. The results indicated that microinjection of mutated annexin 6, in NRK cells, showed the accumulation of LDL in larger e ndocytic structures, denoting retention of LDL in the prelysosomal compartm ent. To confirm the involvement of annexin 6 in the trafficking and the deg radation of LDL we used CHO cells transfected with mutated annexin 6(1-175) . Thus, in agreement with NRK cells the results obtained in CHO cells demon strated a significant inhibition of LDL degradation in CHO cells expressing the mutated form of annexin 6 compared to controls overexpressing wild-typ e annexin 6. Therefore, we conclude that an-nexin 6 is involved in the traf ficking events leading to LDL degradation. (C) 2001 Academic Press.