Alternative titles; symbols
HGNC Approved Gene Symbol: RTN1
Cytogenetic location: 14q23.1 Genomic coordinates (GRCh38): 14:59,595,976-59,870,776 (from NCBI)
Roebroek et al. (1993) described the cloning of a gene, which they designated NSP, that encodes several neuroendocrine-specific proteins. The original cDNA was identified by screening an expression library of the small-cell lung cancer (SCLC) NCI-H82 cell line with antibodies to the previously identified proteins. The gene can produce 3 different transcripts (3.4, 2.3, and 1.8 kb), which are identical at their 3-prime ends but have unique amino termini. The common carboxyl-terminal region contains 2 large hydrophobic domains. The largest cDNA (NSP-A) produces a 135-kD (776-amino acid) protein which is rich in proline and serine residues and contains multiple potential phosphorylation sites. NSP-B and NSP-C have predicted reading frames of 356 and 208 amino acids, respectively. The B transcript was found only in the NCI-H82 cell line. NSP-specific antibodies showed that the proteins are localized to membranes of the endoplasmic reticulum (Senden et al., 1994), leading to their proposed designation as 'reticulons.' Immunohistochemical studies in the rat (van de Velde et al., 1994) showed the presence of NSP-A protein in many regions of the brain. NSP-A or -C transcripts were found in 18 different SCLC lines but not in any of 11 nonendocrine non-SCLCs (van de Velde et al., 1994).
Roebroek et al. (1996) found that the NSP exons are dispersed over a genomic region of about 275 kb. The genomic organization explained the generation of NSP mRNA variants encoding NSP protein isoforms. Multiple promoters rather than alternative splicing of internal exons seemed to be involved in this diversity. Comparison of NSP genomic and cDNA sequences with databank nucleotide sequences resulted in the discovery of other human members of this novel family of reticulon encoding genes. Mannan et al. (2006) noted that RTN1 has 9 exons spanning approximately 295 kb.
Kools et al. (1994) mapped the human NSP gene to chromosome 14q21-q22 by fluorescence in situ hybridization. Mannan et al. (2006) stated that the RTN1 gene maps to chromosome 14q23.1.
By yeast 2-hybrid analysis and coimmunoprecipitation studies in mouse fibroblast cells (NIH3T3) and HeLa cells, Mannan et al. (2006) demonstrated that reticulon-1 interacts with spastin (SPAST; 604277), which is mutated in hereditary spastic paraplegia-4 (SPG4; 182601). The interaction is mediated through the spastin N-terminal region, which contains a microtubule-interacting and trafficking domain. Intracellular distribution studies showed colocalization of the 2 proteins in discrete cytoplasmic vesicles. The findings strengthened the hypothesis that disruption of intracellular vesicular transport processes may underlie spastic paraplegia. Mannan et al. (2006) failed to identify mutations in the coding or flanking intronic sequences of the RTN1 gene in 2 index patients from families with SPG15 (270700), which had been mapped to chromosome 14q.
Kools, P. F. J., Roebroek, A. J. M., van de Velde, H. J. K., Marynen, P., Bullerdiek, J., Van de Ven, W. J. M. Regional mapping of the human NSP gene to chromosome region 14q21-q22 by fluorescence in situ hybridization analysis. Cytogenet. Cell Genet. 66: 48-50, 1994. [PubMed: 8275708] [Full Text: https://doi.org/10.1159/000133662]
Mannan, A. U., Boehm, J., Sauter, S. M., Rauber, A., Byrne, P. C., Neesen, J., Engel, W. Spastin, the most commonly mutated protein in hereditary spastic paraplegia interacts with reticulon 1 an endoplasmic reticulum protein. Neurogenetics 7: 93-103, 2006. [PubMed: 16602018] [Full Text: https://doi.org/10.1007/s10048-006-0034-4]
Roebroek, A. J. M., Ayoubi, T. A. Y., van de Velde, H. J. K., Schoenmakers, E. F. P. M., Pauli, I. G. L., Van de Ven, W. J. M. Genomic organization of the human NSP gene, prototype of a novel gene family encoding reticulons. Genomics 32: 191-199, 1996. [PubMed: 8833145] [Full Text: https://doi.org/10.1006/geno.1996.0105]
Roebroek, A. J. M., van de Velde, H. J. K., Van Bokhoven, A., Broers, J. L. V., Ramaekers, F. C. S., Van de Ven, W. J. M. Cloning and expression of alternative transcripts of a novel neuroendocrine-specific gene and identification of its 135-kDa translational product. J. Biol. Chem. 268: 13439-13447, 1993. [PubMed: 7685762]
Senden, N. H. M., van de Velde, H. J. K., Broers, J. L. V., Timmer, E. D. J., Roebroek, A. J. M., van de Ven, W. J. M., Ramaekers, F. C. S. Cluster-10 lung-cancer antibodies recognize NSPs, novel neuro-endocrine proteins associated with membranes of the endoplasmic reticulum. Int. J. Cancer (Suppl.): 8:-84-88, 1994.
van de Velde, H. J. K., Roebroek, A. J. M., van Leeuwen, F. W., Van de Ven, W. J. M. Molecular analysis of expression in rat brain of NSP-A, a novel neuroendocrine-specific protein of the endoplasmic reticulum. Molec. Brain Res. 23: 81-92, 1994. [PubMed: 7518032] [Full Text: https://doi.org/10.1016/0169-328x(94)90214-3]
van de Velde, H. J. K., Senden, N. H. M., Roskams, T. A. D., Broers, J. L. V., Ramaekers, F. C. S., Roebroek, A. J. M., Van de Ven, W. J. M. NSP-encoded reticulons are neuroendocrine markers of a novel category in human lung cancer diagnosis. Cancer Res. 54: 4769-4776, 1994. [PubMed: 8062278]