Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study describes the molecular characterization of an antigen defined by an autoantibody from a woman with habitual abortion as GM2-activator protein. The patient showed no disorder of renal function. Accidentally with routine serum screening for autoantibodies, an immunoreactivity was found in kidney collecting duct intercalated cells. Three distinct patterns of immunostaining 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 cytoplasmic domain of the vacuolar proton pump in intercalated cells. This pump is subjected to a shuttling mechanism from cytoplasmic stores to the cell membrane, which exclusively occurs in intercalated cells. Peptide sequences of a 23-kD protein purified from rat kidney cortex showed complete identity with corresponding sequences of GM2-activator protein. In the brain, GM2-activator protein is required for hexosaminidase A to split a sugar from ganglioside GM2. Because neither ganglioside GM2 nor GM1 (its precursor) is present in significant amounts in the kidney, the previous finding that this tissue contains the highest level of activator protein in the body was confusing. In this study, a novel role for GM2-activator protein in intercalated cells is proposed, and possible roles in the shuttling mechanism are discussed.
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PMID:Ganglioside GM2-activator protein and vesicular transport in collecting duct intercalated cells. 1007 93

Lysosomal degradation of the ganglioside GM2 by human beta-hexosaminidase A requires the presence of the GM2 activator protein as an essential cofactor. Here we demonstrate that GM2 activator mRNA is differentially expressed and mainly localized to the apical part of the epithelial cells of distal renal tubules and the collecting duct. In order to understand the mechanism underlying the regulation of the GM2 activator gene, we analyzed the genomic organization upstream exon 2 as well as the 5'-flanking region. The GM2 activator gene spans about 16.8 kb with a first intron of 6.5 kb, and the transcription start is located at position -96 upstream from the ATG. DNA elements responsible for GM2 activator expression were identified in a PCR-based method of long-distance DNA walking. Sequence analysis revealed a 2.9 kb region upstream of the ATG that contained regulatory elements like CAAT boxes, Sp1 binding sites as well as AP1, and AP2 sites. Transfection experiments in COS-1 cells with a series of chimeras of 5'-stepwise deletion mutants of the GM2 activator gene 5'-flanking region and the secretory alkaline phosphatase (SEAP)-reporter gene indicated that a genomic fragment encompassing -323 to +1 bp had significant promoter activity. EMSA experiments showed that Sp1 and other transcription factors like AP1, AP2 and CCAAT-Box binding proteins are involved in GM2 activator gene regulation.
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PMID:Characterization of regulatory elements in the 5'-flanking region of the GM2 activator gene. 1098 59