Relationship between novel isoforms, functionally important domains, and subcellular distribution of CD164/endolyn

James Yi Hsin Chan, Jane E. Lee-Prudhoe, Britt Jorgensen, Gudrun Ihrke, Regis Doyonnas, Andrew C.W. Zannettino, Veronica J. Buckle, Christopher J. Ward, Paul J. Simmons, Suzanne M. Watt

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31 Scopus citations

Abstract

Functional analyses have indicated that the human CD164 sialomucin may play a key role in hematopoiesis by facilitating the adhesion of human CD34+ cells to the stroma and by negatively regulating CD34+CD3810/- cell proliferation. We have identified three novel human CD164 variants derived by alternative splicing of bona fide exons from a single genomic transcription unit. The predominant CD164(E1-6) isoform, encoded by six exons, is a type I transmembrane protein containing two extracellular mucin domains (I and II) interrupted by a cysteine-rich non-mucin domain. The 103B2/9E10 and 105A5 epitopes, which specify ligand binding characteristics, are located on the exon 1-encoded mucin domain I. Three human CD164(E1-6) mRNA species, exhibiting differential polyadenylation site usage, are differentially expressed in hematopoietic and non-hematopoietic tissues. This study provides additional evidence that human CD164(E1-6) represents the ortholog of murine MGC-24v and rat endolyn. Comparative analysis of murine MGC-24v/CD164(E1-6) with human CD164(E1-6) revealed two potential splice variants and a similar genomic structure. Whereas the human CD164 gene is located on chromosome 6q21, the mouse gene occurs in a syntenic region on chromosome 10B1-B2. By confocal microscopy, human CD164 in CD34+CD38+ hematopoietic progenitor (KG1B) and epithelial cell lines appears to be localized primarily in endosomes and lysosomes, with low concentrations at the cell surface. However, in a minority of KG1B cells, CD164 is more prominently expressed at the plasma membrane and in the recycling endosomes, suggesting that its distribution is regulated in cells of hematopoietic origin.

Original languageEnglish (US)
Pages (from-to)2139-2152
Number of pages14
JournalJournal of Biological Chemistry
Volume276
Issue number3
DOIs
StatePublished - Jan 19 2001

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chan, J. Y. H., Lee-Prudhoe, J. E., Jorgensen, B., Ihrke, G., Doyonnas, R., Zannettino, A. C. W., Buckle, V. J., Ward, C. J., Simmons, P. J., & Watt, S. M. (2001). Relationship between novel isoforms, functionally important domains, and subcellular distribution of CD164/endolyn. Journal of Biological Chemistry, 276(3), 2139-2152. https://doi.org/10.1074/jbc.M007965200