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] They have also been linked to oligodendrocyte roles in inhibition of neurite outgrowth. Some studies link RTNs with Alzheimer's disease and amyotrophic lateral sclerosis.[2]
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]