Alternative titles; symbols
HGNC Approved Gene Symbol: NRN1
Cytogenetic location: 6p25.1 Genomic coordinates (GRCh38) : 6:5,997,999-6,007,518 (from NCBI)
The NRN1 gene encodes neuritin-1, a GPI-anchored neuronal protein that functions extracellularly to modulate neurite outgrowth. NRN1 is a glutamate and neurotrophin receptor target gene (Naeve et al., 1997).
Using a differential screen of a kainate-activated rat hippocampal dentate gyrus library, Naeve et al. (1997) identified a cDNA encoding neuritin. Using the rat coding sequence as probe, they cloned the human homolog from a cortical cDNA library. The deduced 142-amino acid protein contains a 27-amino acid secretory signal peptide at its N terminus and a 27-amino acid GPI signal peptide at its C terminus. The mature rat and human proteins are 100% identical. Northern blot analysis of rat tissues detected a single 1.6-kb transcript predominantly in brain, with highest expression in the dentate gyrus and lowest expression in the striatum. Northern blot and in situ analyses detected expression of neuritin in developing rat brain at embryonic day 15; the level of expression increased throughout embryonic development and postnatally into adulthood. Neuritin was concentrated on neuronal cell bodies and unevenly dispersed along neuritic projections in the nonmyelinated regions of the brain.
Naeve et al. (1997) demonstrated that neuritin is induced by neural activity and by the activity-regulated neurotrophins BDNF (113505) and NTF3 (162660). Recombinant studies showed that neuritin is a GPI-anchored protein that promotes neurite outgrowth and especially branching of neuritic processes in primary hippocampal and cortical cells.
Son et al. (2012) found that virally-mediated overexpression of Nrn1 in the dorsal hippocampus of Sprague-Dawley rats resulted in increased dendrite complexity and spine density in the dentate gyrus and increased expression of the postsynaptic protein PSD95 (DLG4; 602887). This was associated with improved hippocampus-dependent learning, such as object recognition and contextual fear conditioning, compared to controls.
Stumpf (2025) mapped the NRN1 gene to chromosome 6p25.1 based on an alignment of the NRN1 sequence (GenBank BC002683) with the genomic sequence (GRCh38).
Son et al. (2012) found that virally-mediated gene infusion of neuritin in the hippocampus of Sprague-Dawley rats resulted in improved hippocampus-dependent learning, such as object recognition and contextual fear conditioning, compared to controls. Induction of chronic unpredictable stress (CUS) in mice, a model that can produce or worsen depression (MDD; 608516), resulted in significantly decreased levels of neuritin mRNA in several regions of the hippocampus, and this decrease could be reversed with the antidepressant fluoxetine. Viral expression of Nrn1 in mice significantly decreased the depressive behavioral effects of ongoing CUS, as well as general depressive-like behaviors, similar to antidepressant-like effects. In addition to these behavioral effects, neuritin prevented the CUS-induced spine deficit. However, neuritin did not affect the behaviors produced by prior chronic stress. Knockdown of Nrn1 in the hippocampus produced CUS-like depressive-like behaviors even in the absence of CUS. Son et al. (2012) concluded that the actions of viral neuritin expression are dependent on the type of test and prior stress exposure. Neuritin was sufficient to produce an antidepressant response in models that are responsive to antidepressant administration in unstressed animals. However, there was no effect in models in which the behavioral deficits were produced by prior chronic stress and reversed by antidepressant treatments. Only after CUS exposure did neuritin produce an antidepressant response in these models. These findings indicated that neuritin expression is sufficient to produce an antidepressant response in the absence of stress and to prevent or block the deficits caused by chronic stress exposure, presumably by compensating for the neuritin and synaptogenic deficits caused by stress. The study implicated a role for neuritin in neuroplasticity, particularly in regions involved in depression.
Naeve, G. S., Ramakrishnan, M., Kramer, R., Hevroni, D., Citri, Y., Theill, L. E. Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis. Proc. Nat. Acad. Sci. 94: 2648-2653, 1997. [PubMed: 9122250] [Full Text: https://doi.org/10.1073/pnas.94.6.2648]
Son, H., Banasr, M., Choi, M., Chae, S. Y., Licznerski, P., Lee, B., Voleti, B., Li, N., Lepack, A., Fournier, N. M., Lee, K. R., Lee, I. Y., Kim, J., Kim, J.-H., Kim, Y. H., Jung, S. J., Duman, R. S. Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress. Proc. Nat. Acad. Sci. 109: 11378-11383, 2012. [PubMed: 22733766] [Full Text: https://doi.org/10.1073/pnas.1201191109]
Stumpf, A. M. Personal Communication. Baltimore, Md. 10/31/2025.