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Published on: September 14, 2015
Transport of cationic amino acids by the mouse ecotropic retrovirus receptor
J W Kim1, E I Closs, L M Albritton
1Howard Hughes Medical Institute, Boston, Massachusetts.
Abstract:
Susceptibility of rodent cells to infection by ecotropic murine leukaemia viruses (MuLV) is determined by binding of the virus envelope to a membrane receptor that has multiple membrane-spanning domains. Cells infected by ecotropic MuLV synthesize envelope protein, gp70, which binds to this receptor, thereby preventing additional infections. The consequences of envelope-MuLV receptor binding for the infected host cell have not been directly determined, partly because the cellular function of the MuLV receptor protein is unknown. Here we report a coincidence in the positions of the first eight putative membrane-spanning domains found in the virus receptor and in two related proteins, the arginine and histidine permeases of Saccharomyces cerevisiae (Fig. 1), but not in any other proteins identified by computer-based sequence comparison of the GenBank data base. Xenopus oocytes injected with receptor-encoding messenger RNA show increased uptake of L-arginine, L-lysine and L-ornithine. The transport properties and the expression pattern of the virus receptor behave in ways previously attributed to y+, the principal transporter of cationic L-amino acids in mammalian cells.
Insights
Murine leukemia virus (MuLV) receptors are identified as amino acid transporters. This discovery reveals a novel cellular function for these viral receptors, impacting cell biology and virology.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Susceptibility to ecotropic murine leukemia viruses (MuLV) depends on a specific membrane receptor.
- Infected cells produce envelope protein (gp70) that binds this receptor, blocking further infection.
- The cellular function of the MuLV receptor protein remains largely unknown.
Purpose of the Study:
- To investigate the cellular function of the MuLV receptor protein.
- To identify potential similarities between the MuLV receptor and other known proteins.
- To explore the functional consequences of MuLV receptor-virus binding.
Main Methods:
- Computer-based sequence comparison of the MuLV receptor against the GenBank database.
- Analysis of membrane-spanning domains in the MuLV receptor and related proteins.
- Xenopus oocyte expression system to study receptor function after messenger RNA injection.
Main Results:
- The MuLV receptor shares structural similarities in its membrane-spanning domains with arginine and histidine permeases from Saccharomyces cerevisiae.
- Xenopus oocytes expressing the MuLV receptor exhibited increased uptake of cationic amino acids (L-arginine, L-lysine, L-ornithine).
- The transport characteristics and expression pattern of the MuLV receptor align with known properties of the mammalian cationic amino acid transporter, y+.
Conclusions:
- The MuLV receptor protein functions as a cationic amino acid transporter.
- This finding provides a novel cellular role for a viral receptor.
- The study links viral entry mechanisms to fundamental cellular transport processes.
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