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Reticulons (RTNs in vertebrates and reticulon-like proteins or RNTls in other eukaryotes) are a group of evolutionary conservative proteins residing predominantly in endoplasmic reticulum, primarily playing a role in promoting membrane curvature.[1] In addition reticulons may play a role in nuclear pore complex formation, vesicle formation, and other processes yet to be defined.[2] Some studies link RTNs with Alzheimer's disease and amyotrophic lateral sclerosis.

All eukaryotes studied so far carry RTN genes in their genomes, the reticulons are absent only in archaea and bacteria. Mammals have four reticulon genes, RTN1, RTN2, RTN3, RTN4. Plants possess a greater number of reticulon isoforms, with 21 having been identified in the commonly used model organism Arabidopsis thaliana.[3]

The genes possess a number of exons and introns and are accordingly spliced into many isoforms. C-terminal region of RTNs contains a highly conservative reticulon homology domain (RHD) while other parts of the protein may vary even within a single organism.[2]

A peculiar feature of RTN4's isoform RTN4A (Nogo-A) is its ability to inhibit axonal growth. This reticulon subform is curiously absent in fish,[4] a taxon known for the heightened ability of its CNS to regenerate after injury.

Transmembrane 33 (TMEM33) exogenously suppresses reticulon 4C function and therefore may play a role in dictating membrane curvature through inhibition of reticulon function.[5]


  1. ^ Voeltz, GK; Prinz WA; Shibata Y; Rist JM; Rapoport TA (2006). "A class of membrane proteins shaping the tubular endoplasmic reticulum". Cell. 124 (3): 573–586. PMID 16469703. doi:10.1016/j.cell.2005.11.047. 
  2. ^ a b Yang YS, Strittmatter SM (2007). "The reticulons: a family of proteins with diverse functions". Genome Biol. 8 (12): 234. PMC 2246256Freely accessible. PMID 18177508. doi:10.1186/gb-2007-8-12-234. 
  3. ^ Hawes C, Kiviniemi P, Keichbaumer, V (2015). "The endoplasmic reticulum: A dynamic and well connected organelle". Journal of Integrative Biology. 57: 50–62. PMID 25319240. doi:10.1111/jipb.12297. 
  4. ^ Diekmann H, Klinger M, Oertle T, Heinz D, Pogoda HM, Schwab ME, Stuermer CA (August 2005). "Analysis of the reticulon gene family demonstrates the absence of the neurite growth inhibitor Nogo-A in fish". Mol. Biol. Evol. 22 (8): 1635–48. PMID 15858203. doi:10.1093/molbev/msi158. 
  5. ^ "Identification and Characterization of TMEM33 as a Reticulon-binding Protein" (PDF). Retrieved 2015-02-22. 

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