A 25-aa inhibitory peptide sequence derived from the 66aa active domain; sufficient to produce core inhibitory properties.
Many tissues such as muscle, skin, liver, and peripheral nerve, have remarkable ability to repair and regrowafter injury. However, the CNS (brain and spinal cord) is limited in its ability to repair or regrowth causing permanent brain damage or paralyses. Most recently an inhibitory myelin protein, Nogo (Neurite outgrowth), has been cloned and characterized. It may help block the regeneration of the CNS. Nogo is the 4th member of reticulon (Rtn) family. There are three alternative isoforms of Nogo, designated Nogo-A (full length human protein 1192 aa; calculated mol wt 135kD; rat 1163 aa), an intermediate form Nogo-B (373 aa; ~37 K, lacks 186-1004 aa within the extracellular domain), and a shorter form Nogo-C (199 aa; ~25 K, similar to rat vp20 and foocen-s; lacks 186-1004 aa but which has a smaller, alternative N-terminal domain). Nogo-A has a putative extracellular domain of 1024aa, 2-3 TM domains, and a short C-terminus of 43aa. Nogo-A is localized to the CNS-myelin, and is highly expressed in oligodendorcytes but not by Schwann cells. Nogo-B and Nogo-C have been found in several non-neuronal tissues (skeletal muscle, kidney, skin, lung, and spleen), and it may be the 35-kD protein recognized by IN-1 antibody.
Full length Nogo-A has the strongest inhibitory activity and it may be the 250-kD protein recognized by the IN-1 antibody. The N-terminus of Nogo A is unique, whereas the C-terminus has sequence homology with the reticulon family. Nogo-A has endoplasmic reticulum retention signal sequence. It is not clear how Nogo-A contacts axons, and reaches the membrane of oligodendorcytes. A 66-aa hydrophilic region of Nogo, located between the two TM domains, has the most inhibitory properties of Nogo. In contrast to Nogo, Rtn 1, -2, and 3 do not inhibit axonal regeneration. A 25-aa inhibitory peptide sequence (designated as Nogo-P4; rat Nogo 1056-1080 aa or 31-55aa of the 66aa active peptide) is sufficient to produce core inhibitory properties (see GrandPre T et al (2000). This 66-aa region also has the least similarity to Rtn proteins. The corresponding Rtn-P4 peptide sequence has no activity.