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Gene Review

Sort1  -  sortilin 1

Mus musculus

Synonyms: 2900053A11Rik, AI852375, NTR3, Neurotensin receptor 3, Ntr3, ...
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High impact information on Sort1

  • In 35S-labeled 3T3-L1 adipocytes treated with the cross-linker dithiobis(succinimidyl propionate), lipoprotein lipase-containing complexes were isolated by anti-sortilin antibodies [1].
  • The binding was inhibited by heparin and RAP and by the newly discovered sortilin ligand neurotensin [1].
  • In conclusion, ASM uses sortilin as an alternative receptor to be targeted to the lysosomes [2].
  • Furthermore, over-expression of truncated sortilin accelerated and enhanced the secretion of ASM from COS-7 cells and I-cells [2].
  • The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor [2].

Biological context of Sort1


Anatomical context of Sort1

  • Here, we demonstrate that the cloned mouse NTR3 is expressed on the plasma membrane of transfected COS-7 cells [6].
  • This investigation demonstrated that sortilin was required for the trafficking of prosaposin to the lysosomes in TM4 cells [3].
  • Using a TM4 Sertoli cell line, we tested the hypothesis that prosaposin and GM2AP are targeted to the lysosomal compartment via the sortilin receptor, which has been recently shown to have a GGA binding motif [7].
  • Sortilin (approximately 95 kDa) is a member of the recently discovered family of Vps10p-domain receptors, and is expressed in a variety of tissues, notably brain, spinal cord and muscle [8].

Associations of Sort1 with chemical compounds

  • Knockdown of sortilin decreases both formation of GSVs and insulin-regulated glucose uptake [5].
  • Sortilin, a type I transmembrane glycoprotein that belongs to a novel family of receptor proteins, presents structural features of receptors involved in lysosomal targeting [2].

Physical interactions of Sort1

  • Biochemical analysis and confocal microscopic imaging clearly indicate that NT is efficiently internalized after binding to NTR3, and that despite this internalization, the amount of receptor present on the cell surface is maintained [6].

Regulatory relationships of Sort1


Other interactions of Sort1


Analytical, diagnostic and therapeutic context of Sort1

  • The mouse NTR3 is detectable by photoaffinity labeling and immunoblotting at the cell surface as a 100 kDa N-glycosylated protein [6].
  • Co-immunoprecipitation assays confirmed the interaction between sortilin and ASM [2].
  • Confocal microscopy revealed that truncated sortilin partially inhibited the lysosomal trafficking of ASM in COS-7 cells and abolished the lysosomal targeting of ASM in I-cells [2].


  1. Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. Nielsen, M.S., Jacobsen, C., Olivecrona, G., Gliemann, J., Petersen, C.M. J. Biol. Chem. (1999) [Pubmed]
  2. The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor. Ni, X., Morales, C.R. Traffic (2006) [Pubmed]
  3. Study of the mouse sortilin gene: Effects of its transient silencing by RNA interference in TM4 Sertoli cells. Zeng, J., Hassan, A.J., Morales, C.R. Mol. Reprod. Dev. (2004) [Pubmed]
  4. Expression of the 100-kDa neurotensin receptor sortilin during mouse embryonal development. Hermans-Borgmeyer, I., Hermey, G., Nykjaer, A., Schaller, C. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  5. Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes. Shi, J., Kandror, K.V. Dev. Cell (2005) [Pubmed]
  6. Pharmacological properties of the mouse neurotensin receptor 3. Maintenance of cell surface receptor during internalization of neurotensin. Navarro, V., Martin, S., Sarret, P., Nielsen, M.S., Petersen, C.M., Vincent, J., Mazella, J. FEBS Lett. (2001) [Pubmed]
  7. The trafficking of prosaposin (SGP-1) and GM2AP to the lysosomes of TM4 Sertoli cells is mediated by sortilin and monomeric adaptor proteins. Hassan, A.J., Zeng, J., Ni, X., Morales, C.R. Mol. Reprod. Dev. (2004) [Pubmed]
  8. Sortilin is essential for proNGF-induced neuronal cell death. Nykjaer, A., Lee, R., Teng, K.K., Jansen, P., Madsen, P., Nielsen, M.S., Jacobsen, C., Kliemannel, M., Schwarz, E., Willnow, T.E., Hempstead, B.L., Petersen, C.M. Nature (2004) [Pubmed]
  9. Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line. Dicou, E., Vincent, J.P., Mazella, J. J. Neurosci. Res. (2004) [Pubmed]
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