8.A.102.  The Reticulon (Reticulon) Family

Primary plant plasmodesmata (PD) arise at cytokinesis when the new cell plate forms. During this process, fine strands of endoplasmic reticulum (ER) are laid down between enlarging Golgi-derived vesicles to form nascent PD, each pore containing a desmotubule, a membranous rod derived from the cortical ER. Members of the reticulon (RTNLB) family of ER-tubulating proteins in Arabidopsis thaliana play a role in the formation of the desmotubule. RTNLB3 and RTNLB6, two RTNLBs present in the PD proteome, are recruited to the cell plate at late telophase, when primary PD are formed, and remain associated with primary PD in the mature cell wall (Knox et al. 2015). Both RTNLBs show significant colocalization at PD. These RTNLBs are mobile at the edge of the developing cell plate where new wall materials are being delivered, but significantly less mobile at its center, where PD are forming. Reticulons are involved in peroxysomal biogenesis (Mast et al. 2016). Reticulon proteins regulate intracellular trafficing in plants (Lee et al. 2011).  RTN3 is directly involved in the ER-constituent trafficking events through dually acting as an essential and important ER-stress sensor, and a trigger for Bcl-2 translocation (Wan et al. 2007). 

Reticulons are within a large family of integral membrane proteins that are ubiquitous in eukaryotes and play a key role in functional remodelling of the endoplasmic reticulum membrane. The reticulon family is especially large in plants, with the Arabidopsis thaliana genome containing twenty-one isoforms. Reticulons vary in length but all contain a conserved C-terminal reticulon homology domain (RHD) that associates with membranes.  The structure of one small homologue has been modeled (Chow et al. 2018).

This family belongs to the .



Chow, M., M. Sklepari, L. Frigerio, and A.M. Dixon. (2018). Bacterial expression, purification and biophysical characterization of the smallest plant reticulon isoform, RTNLB13. Protein Expr Purif 152: 31-39. [Epub: Ahead of Print]

Hu, J. and T.A. Rapoport. (2016). Fusion of the endoplasmic reticulum by membrane-bound GTPases. Semin Cell Dev Biol 60: 105-111.

Knox, K., P. Wang, V. Kriechbaumer, J. Tilsner, L. Frigerio, I. Sparkes, C. Hawes, and K. Oparka. (2015). Putting the Squeeze on Plasmodesmata: A Role for Reticulons in Primary Plasmodesmata Formation. Plant Physiol. 168: 1563-1572.

Lee, H.Y., C.H. Bowen, G.V. Popescu, H.G. Kang, N. Kato, S. Ma, S. Dinesh-Kumar, M. Snyder, and S.C. Popescu. (2011). Arabidopsis RTNLB1 and RTNLB2 Reticulon-like proteins regulate intracellular trafficking and activity of the FLS2 immune receptor. Plant Cell 23: 3374-3391.

Mallmann, R., K. Ondacova, L. Moravcikova, B. Jurkovicova-Tarabova, M. Pavlovicova, L. Lichvarova, V. Kominkova, N. Klugbauer, and L. Lacinova. (2019). Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated Ca2.2 Ca channels. Pflugers Arch. [Epub: Ahead of Print]

Mast, F.D., A. Jamakhandi, R.A. Saleem, D.J. Dilworth, R.S. Rogers, R.A. Rachubinski, and J.D. Aitchison. (2016). Peroxins Pex30 and Pex29 Dynamically Associate with Reticulons to Regulate Peroxisome Biogenesis from the Endoplasmic Reticulum. J. Biol. Chem. 291: 15408-15427.

Wan, Q., E. Kuang, W. Dong, S. Zhou, H. Xu, Y. Qi, and Y. Liu. (2007). Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to endoplasmic reticulum stress. Apoptosis 12: 319-328.


TC#NameOrganismal TypeExample

Reticulon-like protein B6 of 253 aas and 4 TMSs, RTNLB6.

RTNLB6 of Arabidopsis thaliana (Mouse-ear cress)


Reticulon-3, Rtn3, of 964 aas and 3 - 4 TMSs at the C-terminus of the protein. May be involved in membrane trafficking in the early secretory pathway. Rtn3 inhibits BACE1 activity and amyloid precursor protein processing and may induce the caspase-8 cascade and apoptosis. May also favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress, and induces the formation of endoplasmic reticulum tubules (Yamamoto et al. 2014).

Rtn3 of Mus musculus (Mouse)


Reticulon-1 isoform X2, Rtn1, of 433 aas and 4 TMSs.

Rtn1 of Apis mellifera


Reticulon-like protein 1, RTN1 of 295 aas and 2 or 4 TMSs.

RTN1 of Saccharomyces cerevisiae (Baker's yeast)


Reticulon-like protein of 216 aas and 4 TMSs.

RTN protein of Pfiesteria piscicida (Dinoflagellate)


Reticulon-3B, RTN3B, isoform X5 of 220 aas and 4 TMSs

RTN3B protein of Oryzias latipes (Japanese rice fish;Japanese killifish)


Reticulon-like protein B13, RTNLB13, of 206 aas and 4 TMSs, the smallest of the 21 reticulon-like proteins in A. thaliana (Chow et al. 2018).

RTNBLB13 of Arabidopsis thaliana (Mouse-ear cress)


Reticulon-like protein 2, RTN2, of 393 aas and 2, 3 or 4 TMSs.  Functioins together with Sey1 (TC# 1.N.5.1.6) as well as RTN1 (TC# 8.A.102.1.4), YOP1 of the DP1 family and LNP1 (P38878) to promote ER membrane fusion and reorganization (Hu and Rapoport 2016).

RTN2 of Saccharomyces cerevisiae (Baker's yeast)


Reticulon 1, RTN1 or NSP, of 776 aas and 2 C-terminal TMSs.  Regluates calcium channel CaV2.2 by direct interaction with domain 4 (Mallmann et al. 2019).

RTN1 of Homo sapiens


TC#NameOrganismal TypeExample

ER membrane reticulon-like protein of 202 aas and 4 TMSs

RTNL protein of Tetrahymena thermophila


Uncharacterized protein of 180 aas and 4 TMSs.

UP of Plasmodium malariae


Putative reticulon domain-containing protein of 219 aas and 4 TMSs.

Reticulon of Eimeria acervulina (Coccidian parasite)


Uncharacterized protein of 188 aas and 4 TMSs.

UP of Theileria equi


Uncharacterized protein of 183 aas and 4 TMSs.

UP of Cryptosporidium hominis