Annexin A6 is recruited into lipid rafts of Niemann–Pick type C disease fibroblasts in a Ca2+-dependent manner

Niemann–Pick type C (NPC) disease is characterized by excessive accumulation of cholesterol in the late endosome/lysosome compartment. Some members of the annexin family of proteins such as annexin A2 (AnxA2) and annexin A6 (AnxA6) follow the same route as cholesterol during the endocytic pathway and are found, as AnxA6, attached to the membranes of the cholesterol storage compartment in NPC disease fibroblasts. Therefore, the purpose of this work was to test the hypothesis that AnxA6 participates in the NPC-induced changes in the organization of membrane microdomains resistant to solubilization by a nonionic detergent, Triton X-100, i.e., detergent-resistant microdomains (DRMs). Using cellular fractionation, fluorescence microscopy and specific antibodies we observed that in the absence of calcium AnxA6 was found in the DRM-depleted membrane fractions isolated from NPC and control fibroblasts. In the presence of calcium, AnxA6 re-located to the fractions enriched in DRMs only in the NPC cells, suggestive of AnxA6 participation in organization of these microdomains.

Research highlights
► Niemann–Pick type C (NPC) disease is characterized by accumulation of cholesterol.
► Annexin A2 and annexin A6 (AnxA6) follow cholesterol during the endocytic pathway.
► AnxA6 is attached to the cholesterol storage compartment in NPC fibroblasts.
► AnxA6 participates in organization of membrane microdomains, DRMs, in NPC cells.
► In the presence of calcium, AnxA6 re-locates to DRMs only in NPC cells.