Disease relevance of RTN1

• Reticulon proteins: emerging players in neurodegenerative diseases [1].
• NSP-encoded reticulons are neuroendocrine markers of a novel category in human lung cancer diagnosis [2].
• Maternal hypothyroidism selectively affects the expression of neuroendocrine-specific protein A messenger ribonucleic acid in the proliferative zone of the fetal rat brain cortex [3].
• RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate [4].
• The rubella virus (RUB) nonstructural (NS) protein (NSP) ORF encodes a protease that cleaves the NSP precursor (240 kDa) at a single site to produce two products [5].

Psychiatry related information on RTN1

• The hypothesis was that stem cell proliferation is reduced in affective disorders, and that antidepressant treatment increases NSP [6].
• Neuroendocrine-specific protein C, a marker of neuronal differentiation, is reduced in brain of patients with Down syndrome and Alzheimer's disease [7].
• There are reports on effects of energy intake and expenditure, alcohol consumption, intakes of total fat, different fatty acids, fish oil, NSP and vitamins on markers of coagulation, platelet function and fibrinolysis [8].

High impact information on RTN1

• Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate [4].
• Here we show that reticulon family members are binding partners of BACE1 [9].
• An increase in the expression of any reticulon protein substantially reduces the production of Abeta [9].
• Thus, changes in the expression of reticulon proteins in the human brain are likely to affect cellular amyloid-beta and the formation of amyloid plaques [9].
• Here we identify Nogo as a member of the Reticulon family, Reticulon 4-A [10].

Chemical compound and disease context of RTN1

• Dibutyryl cyclic adenosine monophosphate treatment does increase NSP levels in mouse neuroblastoma cells, but not to the levels expected for fully differentiated neurons [11].

Biological context of RTN1

• The presence of alternative promoters for gene expression and multiple cryptic splicing sites have resulted in large numbers of genes/proteins that are classified among the reticulon family [1].
• In mammalian genomes, transcripts are produced from four genes, rtn1 to rtn4, under the regulation of tissue or cell-type-specific expression [1].
• The last 6 exons, which are present in both transcripts, share significant amino acid sequence identity with the endoplasmic reticulum-bound portion of NSP [12].
• Reticulon 4-A is under intense investigation because of its inhibitory effect on neurite outgrowth, and reticulon 4-B has been suggested to induce apoptosis [13].
• Transient expression assays with a set of human PC1 gene fragments containing progressive 5' deletions demonstrate that the proximal promoter region is capable of directing high levels of neuroendocrine-specific expression of reporter gene constructs [14].

Anatomical context of RTN1

• Two hydrophobic subregions are present, which are thought to be responsible for the association of the RTN1 and RTN2 proteins with the endoplasmic reticulum [15].
• Analysis of the reticulon gene family demonstrates the absence of the neurite growth inhibitor Nogo-A in fish [16].
• In contrast to Nogo, Reticulon 1 and 3 are not expressed by oligodendrocytes, and the 66-residue lumenal/extracellular domains from Reticulon 1, 2 and 3 do not inhibit axonal regeneration [10].
• The NSP transcript encoding NSP-B was found only in SCLC cell line NCI-H82 [2].
• In Purkinje cells, we found NSP-immunostaining in the perikaryon, the extensive dendritic tree and the axon, also suggesting association with the smooth endoplasmic reticulum [17].

Associations of RTN1 with chemical compounds

• The data implicate a novel ER localization mechanism for this neuroendocrine-specific luminal ER resident [18].
• The ASYIP protein contains two hydrophobic regions and a double lysine endoplasmic reticulum (ER) retrieval motif at its C-terminus, which was shown to be identical to RTN3, a reticulon family protein of unknown function [19].
• Identification of neuroendocrine-specific protein as an ethanol-regulated gene with mRNA differential display [20].
• MIS inhibited the proliferation of both SP and NSP cells, whereas the lipophilic chemotherapeutic agent doxorubicin more significantly inhibited the NSP cells [21].
• Rab3A is a neural/neuroendocrine-specific member of the Rab family involved in Ca(2+) -regulated exocytosis, where it functions in an inhibitory capacity controlling recruitment of secretory vesicles into a releasable pool at the plasma membrane [22].

Physical interactions of RTN1

• Using in vitro and in vivo immunoprecipitation experiments, we were able to demonstrate that RTN1 interacts specifically with spastin [23].

Other interactions of RTN1

• Like the RTN1 gene, the RTN2 gene is transcribed into different mRNA variants [15].
• By using the yeast two-hybrid system, we have identified a member of the reticulon (RTN) family (RTN-1C) as the major GCS-protein partner [24].
• It is interesting to note that RTN1 is localized to 14q23.1 where SPG15 locus was mapped [23].
• The hypothesis that Nogo-A (Reticulon 4A) and Nogo-66 receptor (NgR1) limit adult CNS axonal growth after injury is supported by both in vitro experiments and in vivo pharmacological studies [25].
• Spastin mediates its interaction with RTN1 through its N-terminal region containing a microtubule-interacting and trafficking domain [23].

Analytical, diagnostic and therapeutic context of RTN1

• Neuroendocrine-specific protein (NSP) reticulons are expressed in neural and neuroendocrine tissues and cell cultures derived therefrom, while most other cell types lack NSP-reticulons [26].
• Western blot analysis confirmed the presence of NSP-reticulon expression in these non-SCLC-NE cell lines, and showed that they were predominantly of the NSP-A type [27].
• Regional mapping of the human NSP gene to chromosome region 14q21-->q22 by fluorescence in situ hybridization analysis [28].
• The calculated energy excretion from the stoma was three times higher after flaked than after milled barley [51.5 decreasing to 15.3 kJ/g nonstarch polysaccharide (NSP, P < 0.001] [29].
• Sequence analysis has revealed structures within the 3'-UTR that are conserved in these mRNAs and human NSP mRNA and that could be involved in specific compartmentalization of s-rex/NSP mRNA in neuronal cells [30].

References