Receptor extracellular domains may contain trafficking information

Studies of the 300-kDa mannose 6-phosphate receptor

Suzanne M. Dintzis, Victor E Velculescu, Suzanne R. Pfeffer

Research output: Contribution to journalArticle

Abstract

The 300-kDa mannose 6-phosphate receptor cycles between the trans Golgi network and late endosomes, and between the plasma membrane and early endosomes, to deliver lysosomal enzymes to prelysosomes. Mannose 6-phosphate receptor trafficking requires structural determinants present in the cytoplasmic domain. However, when this domain was joined with the extracellular and transmembrane domains of the epidermal growth factor receptor, it was not sufficient to direct this chimera to late endosomes and the trans Golgi network (Dintzis, S. M., and Pfeffer, S. R. (1990) EMBO J. 9, 77-84). These findings suggested a role for extracellular and/or transmembrane domains in mannose 6-phosphate receptor trafficking. We describe here the construction and expression of chimeric receptors comprised of mannose 6-phosphate receptor extracellular and transmembrane sequences joined with cytoplasmic domain sequences derived from the human epidermal growth factor receptor or the human low density lipoprotein receptor. The chimeras were stable proteins which were efficiently endocytosed and competent to bind a mannose 6-phosphate-containing ligand. Antibody binding assays and indirect immunofluorescence showed that the chimeras containing the mannose 6-phosphate receptor extracellular domain colocalized with mannose 6-phosphate receptors in intracellular compartments. These experiments suggest that the presence of the mannose 6-phosphate receptor extracellular domain may interfere with the rapid recycling of receptors from early endosomes to the cell surface and detain receptors within endosomes.

Original languageEnglish (US)
Pages (from-to)12159-12166
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number16
StatePublished - Apr 22 1994
Externally publishedYes

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IGF Type 2 Receptor
Endosomes
trans-Golgi Network
Epidermal Growth Factor Receptor
Cell Surface Receptors
Cell membranes
Indirect Fluorescent Antibody Technique
Endocytosis
Recycling
Assays
Cell Membrane
Ligands
Antibodies
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Receptor extracellular domains may contain trafficking information : Studies of the 300-kDa mannose 6-phosphate receptor. / Dintzis, Suzanne M.; Velculescu, Victor E; Pfeffer, Suzanne R.

In: Journal of Biological Chemistry, Vol. 269, No. 16, 22.04.1994, p. 12159-12166.

Research output: Contribution to journalArticle

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