RTN2 (Reticulon-2), also known as Nogo, is a member of the reticulon family with roles in ER organization and inhibition of neurite outgrowth. RTN2 is a potent axonal growth inhibitor expressed in the central nervous system myelin. The Nogo-66 domain interacts with the Nogo receptor (NgR) to block regeneration after injury.
Reticulon-2 (RTN2), also known as Nogo, is a member of the reticulon family most famous for its role as an inhibitor of axonal regeneration in the central nervous system.
RTN2 contains:
- N-terminal reticulon homology domain (RHD)
- Long hydrophobic domains for membrane association
- Nogo-66 domain (66 amino acids) - the extracellular/intracellular loop
- N-terminal region (Nogo-A specific)
Multiple isoforms: Nogo-A, Nogo-B, Nogo-C
- Axon regeneration inhibition - Nogo-A (RTN2-A) is a potent inhibitor of axonal regeneration
- Myelin formation - Expressed by oligodendrocytes
- ER morphology - Shapes ER network
- Neuronal development - May affect neuronal differentiation
RTN2 is expressed in oligodendrocytes, neurons, and some non-neural tissues.
- Nogo-A is a major barrier to regeneration after SCI
- Anti-Nogo antibodies promote functional recovery in animal models
- Nogo receptor (NgR) blocking enhances axon sprouting
- Nogo-A may affect remyelination
- Therapeutic targeting under investigation
- May affect neuronal connectivity
- Possible role in synaptic plasticity
- Altered expression in motor neurons
- May affect axonal integrity
- Anti-Nogo antibodies - Promoted in clinical trials for spinal cord injury
- NgR antagonists - Blocking Nogo signaling
- Vaccination approaches - Anti-Nogo immunotherapy
RTN2 interacts with:
- Nogo receptor (RTN4R/NgR1)
- PirB receptor
- BCR/ABL
- ER shaping proteins
- Schwab & Strittmatter, Nogo limits neural plasticity (2014)
- GrandPre et al., Nogo-66 receptor (2000)