Ganglioside GM2-activator protein and vesicular transport in collecting duct intercalated cells

This study describes the molecular characterization of an antigen defined b y an autoantibody from a woman with habitual abortion as GM2-activator prot ein. The patient showed no disorder of renal function. Accidentally with ro utine serum screening for autoantibodies, an immunoreactivity was found in kidney collecting duct intercalated cells. Three distinct patterns of immun ostaining of intercalated cells were observed: staining of the apical pole, basolateral pole, and diffuse cytoplasmic labeling. Ultrastructurally, the immunoreactivity was associated with "studs," which represent the cytoplas mic domain of the vacuolar proton pump in intercalated cells. This pump is subjected to a shuttling mechanism from cytoplasmic stores to the cell memb rane, which exclusively occurs in intercalated cells. Peptide sequences of a 23-kD protein purified from rat kidney cortex showed complete identity wi th corresponding sequences of GM2-activator protein. In the brain, GM2-acti vator protein is required for hexosaminidase A to split a sugar from gangli oside GM2. Because neither ganglioside GM2 nor GM1 (its precursor) is prese nt in significant amounts in the kidney, the previous finding that this tis sue contains the highest level of activator protein in the body was confusi ng. In this study, a novel role for GM2-activator protein in intercalated c ells is proposed, and possible roles in the shuttling mechanism are discuss ed.