Transthyretin interacts with the lysosome-associated membrane protein (LAMP-1) in circulation

M. H Y Chang, Chi T. Hua, Elizabeth L. Isaac, Tom Litjens, Greg Hodge, Litsa E. Karageorgos, Peter J. Meikle

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

LAMP-1 (lysosome-associated membrane protein), a major glycoprotein present in the lysosomal membrane, constitutes up to 50% of total membrane proteins. LAMP-1, expressed at the plasma membrane, is reported to be the major molecule expressing the sialyl-Lewis X antigen. Two forms of LAMP-1 exist; the full-length LAMP-1 [LAMP-1 (+Tail)] has a highly glycosylated lumenal domain, a membrane-spanning domain and a short cytoplasmic tail, and the truncated LAMP-1 [LAMP-1 (-Tail)] contains only the lumenal domain. Soluble LAMP-1 (±Tail) has been reported in circulation. LAMP-1 at the cell surface has been shown to interact with E-selectin and galectin and is proposed to function in cell-cell interactions. However, the functional role(s) of soluble LAMP-1 in circulation is unclear. To investigate the functional role of soluble LAMP-1 in circulation, recombinant LAMP-1 (-Tail) and LAMP-1 (+Tail) were produced in HT1080 cells. Two immune-quantification assays were developed to distinguish between the LAMP-1 forms. The interaction and aggregation properties of the different LAMP-1 forms were investi gated using the immune-quantification assays. Only LAMP-1 (+Tail) was found to aggregate and interact with plasma proteins. Plasma proteins that interact with LAMP-1 were isolated by affinity chromatography with either the recombinant LAMP-1 (-Tail) or a synthesized peptide consisting of the 14 amino acids of the LAMP-1 cytoplasmic tail. Transthyretin was found to interact with the cytoplasmic tail of LAMP-1. Transthyretin exists as a homotetramer in plasma, as such may play a role in the aggregation of LAMP-1 in circulation.

Original languageEnglish
Pages (from-to)481-489
Number of pages9
JournalBiochemical Journal
Volume382
Issue number2
DOIs
Publication statusPublished - 1 Sep 2004

Keywords

  • Affinity chromatography
  • Lysosome-associated membrane protein (LAMP-1)
  • Plasma protein
  • Transthyretin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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