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Gene Review

RFT1  -  RFT1 homolog (S. cerevisiae)

Homo sapiens

Synonyms: CDG1N, Protein RFT1 homolog
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High impact information on RFT1

  • These studies, done with N(5)-methyltetrahydrofolate (the predominant folate derivative in blood) and folate as substrates, have shown that RFT-1 functions in a Na(+)- and C1(-)-independent manner [1].
  • NO is elevated in diabetes, and therefore in the present study the alteration of RFT-1 activity in RPE under conditions of high glucose was investigated [2].
  • Nitric oxide (NO) significantly decreases the activity of RFT-1 in cultured RPE cells [2].
  • METHODS: Human ARPE-19 cells were incubated in media containing 5 mM glucose plus 40 mM mannitol (control) or 45 mM glucose for varying periods and the activity of RFT-1 was assessed by determining the uptake of [3H]-N(5)-methyltetrahydrofolate (MTF) [2].
  • The activity of RFT-1 and expression of mRNA encoding RFT-1 were analyzed also in RPE of streptozotocin-induced diabetic mice [2].

Anatomical context of RFT1

  • However, a cocktail of three ITs prepared from RFT11, WT1 and RFT1 gave superior and consistent killing (mean 99.9%; range 99.8-100%) of peripheral blood T cells from six donors [3].
  • In RPE, RFT-1 is localized to the apical membrane and is thought to transport folate from RPE to photoreceptor cells [4].
  • Treatment of ARPE-19 cells, a human RPE cell line, with Hcy at concentrations higher than 50 microM led to a significant decrease in RFT-1 activity [4].
  • The differential polarized distribution of the folate receptor alpha (FR alpha) in the basal membrane and reduced-folate transporter (RFT-1) in the apical membrane was demonstrated previously in the retinal pigment epithelium (RPE) [5].

Associations of RFT1 with chemical compounds


Physical interactions of RFT1

  • The presence of FR alpha in the basal membrane was demonstrable by folate binding and that of RFT-1 in the apical membrane by blockade of folate transport by RFT-1-specific antibody [5].

Other interactions of RFT1

  • The immunotoxin prepared from RFT1 (CD5) was the next most efficient toxin and the immunotoxin prepared from RFT8 (CD8) was the least toxic [3].
  • CONCLUSIONS: Excess folate levels downregulate RFT-1 in RPE [6].
  • Based on this, we hypothesized that folate would enter the RPE via FR alpha and exit the cell via RFT-1 [5].

Analytical, diagnostic and therapeutic context of RFT1

  • Laser-scanning confocal microscopy using antibodies specific for RFT-1 demonstrated an apical distribution of this protein in cultured human and intact mouse RPE, which contrasts with the basolateral distribution of FRalpha in these cells [1].
  • Semiquantitative RT-PCR demonstrated that the mRNA encoding RFT-1 was decreased significantly in RPE of diabetic mice [2].
  • The levels of mRNA encoding RFT-1 were determined by RT-PCR and protein levels by Western blot analysis [2].


  1. Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium. Chancy, C.D., Kekuda, R., Huang, W., Prasad, P.D., Kuhnel, J.M., Sirotnak, F.M., Roon, P., Ganapathy, V., Smith, S.B. J. Biol. Chem. (2000) [Pubmed]
  2. Downregulation of reduced-folate transporter by glucose in cultured RPE cells and in RPE of diabetic mice. Naggar, H., Ola, M.S., Moore, P., Huang, W., Bridges, C.C., Ganapathy, V., Smith, S.B. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  3. Elimination of T cells from human peripheral blood and bone marrow using a cocktail of three anti-T cell immunotoxins. Katz, F.E., Janossy, G., Cumber, A., Ross, W., Blacklock, H.A., Tax, W., Thorpe, P.E. Br. J. Haematol. (1987) [Pubmed]
  4. Regulation of reduced-folate transporter-1 (RFT-1) by homocysteine and identity of transport systems for homocysteine uptake in retinal pigment epithelial (RPE) cells. Naggar, H., Fei, Y.J., Ganapathy, V., Smith, S.B. Exp. Eye Res. (2003) [Pubmed]
  5. Transcellular transfer of folate across the retinal pigment epithelium. Bridges, C.C., El-Sherbeny, A., Ola, M.S., Ganapathy, V., Smith, S.B. Curr. Eye Res. (2002) [Pubmed]
  6. Regulation of reduced-folate transporter-1 in retinal pigment epithelial cells by folate. Naggar, H., Van Ells, T.K., Ganapathy, V., Smith, S.B. Curr. Eye Res. (2005) [Pubmed]
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