PMC

The expression and function of reticulons. (a) Myc-tagged reticulon constructs transfected into COS-7 cells show a reticular expression pattern. Scale bar, 70 μm. (b) Proteins known to interact with ER-associated and intracellular reticulons and their possible intracellular roles. Some classes of proteins may overlap in their cellular functions.

The structure and membrane topology of reticulons. (a) Structure of reticulon proteins. Numbers refer to the exons that encode the protein regions. Black ovals represent hydrophobic regions. GenBank accession numbers are as in Figure 1. (b) Possible topologies of reticulon proteins in membranes. Although eight or more conformations are possible, only those for which evidence exists are depicted. Different topologies in different cell types and different membranes may enable reticulons to carry out diverse roles in the cell.

Interaction of Nogo-A with Nogo receptor. The interaction of Nogo-A (RTN4A) on oligodendrocytes and the Nogo receptor (NogoR) on neurons results in inhibition of axon regeneration after injury via Rho signaling [17,23,55,59,61-63,79]. The different regions of Nogo-A are colored as follows: red, 66-loop (Nogo66); green, Nogo-A-24; blue, Δ20. NogoR is in orange. The 66-loop interacts with NogoR to mediate growth-cone collapse and neurite outgrowth in vitro and to inhibit axon regeneration after injury [21,23,25,53,56,58,60,62]. The amino-terminal region Nogo-A-24 increases the binding affinity of Nogo-A to NogoR and also binds NogoR directly [15]. The amino-terminal region Δ20 can mediate fibroblast and growth-cone collapse independently of NogoR [16]. Some known co-receptors and signal transducers are listed beside the yellow symbol and are described in more detail in Table 1.

Phylogenetic analysis of the reticulon homology domains (RHDs) of selected RTNs and RTNLPs. Alignments were created using the ClustalW2 program [99] and the tree was generated with Phylo_win software [100]. Bootstrap numbers are shown; the number of repetitions was 1,000. The tree was generated using the maximum likelihood method. GenBank accession numbers are as follows: H. sapiens RTN1A, NP_066959; H. sapiens RTN2A, NP_005610; H. sapiens RTN3A, NP_006045; H. sapiens RTN4A, NP_065393; M. musculus RTN1A, NP_703187; M. musculus RTN2B, NP_038676; M. musculus RTN3A, NP_001003934; M. musculus RTN4A, NP_918943; G. gallus RTN4, NP_989697; X. laevis RTN2A, NP_001089014; X. laevis RTN4, NP_001083238; D. rerio RTN4, NP_001018620; D. melanogaster Rtnl1A, NP_787987; C. elegans RET-1, NP_506656; S. cerevisiae RTNLA, NP_010077; A. thaliana RTNLB3, NP_176592.