Disease relevance of ITM2B

• Determining the precise molecular pathways affected by the specific binding between APP and BRI2 could result in the identification of common therapeutic targets for these sporadic and familial neurodegenerative disorders [1].
• The data presented here and the abundance of pGlu peptides in amyloidoses, such as FBD and AD, suggest pGlu-amyloid peptides as a species with biophysical characteristics that might be in particular crucial for the initiation of the disease [2].
• Worth noting is that expression of wild-type British or Danish mutants of BRI2, in mouse neuroblastoma N2a cells that do not express endogenous BRI2, induces elongation of neurites, which suggests a role for this protein in differentiation of neuronal cells [3].
• The biosynthesis of the HLA-A and -B antigens was studied in the B lymphoblastoid cell line BRI 8 and the Burkitt lymphoma line DAudi [4].
• Familial British dementia (FBD), pathologically characterized by cerebral amyloid angiopathy (CAA), amyloid plaques, and neurofibrillary degeneration, is associated with a stop codon mutation in the BRI gene resulting in the production of an amyloidogenic fragment, amyloid-Bri (ABri) [5].

Psychiatry related information on ITM2B

• Notably, BRI2 mutations cause familial British (FBD) and Danish dementias (FDD) that are clinically and pathologically similar to AD [6].
• While a physiological role of BRI in brain remains to be determined, the behavior of BRI in diverse brain lesions appears to be somewhat analogous to that of amyloid precursor protein, which is the source of the beta-amyloid protein of Alzheimer's disease [7].

High impact information on ITM2B

• BRI-ghtening the pathway to steroid hormone signaling events in plants [8].
• A stop-codon mutation in the BRI gene associated with familial British dementia [9].
• A point mutation at the stop codon of BRI therefore results in the generation of the ABri peptide, which is deposited as amyloid fibrils causing neuronal disfunction and dementia [9].
• This highly insoluble peptide is a fragment of a putative type-II single-spanning transmembrane precursor that is encoded by a novel gene, BRI, located on chromosome 13 [9].
• Molecular genetic analysis of the BRI gene in the Danish kindred showed a different defect, namely the presence of a 10-nt duplication (795-796insTTTAATTTGT) between codons 265 and 266, one codon before the normal stop codon 267 [10].

Biological context of ITM2B

• ITM2B that showed a significant association (P < 0.005) between expression and LOH at the corresponding locus could, furthermore, be the main target of the observed LOH at 13q in prostate tumors [11].
• Patients with FBD have a single nucleotide substitution at codon 267 in the BRI2 gene, resulting in an arginine replacing the stop codon and a longer open reading frame of 277 amino acids instead of 266 [12].
• BMD increased with pubertal maturation from 0.68 +/- 0.08 to 0.92 +/- 0.09 g/cm2 (vertebral bone density, VBD) and from 0.87 +/- 0.10 to 1.03 +/- 0.09 g/cm2 (femoral bone density, FBD) between Tanner stage 1 and 5 [13].
• The breathing reserve index (BRI = minute ventilation/maximal voluntary ventilation) at the lactate threshold (LT) is a predictor of a pulmonary mechanical limit to incremental exercise [14].
• Relative risks from the multivariate model included (95% confidence interval in parentheses) BRI at LT, 17.52 (2.45-123.97); resting Pa(CO(2)), 1.29 (1.10-1.49); resting Pa(O(2)), 0.97 (0.90-1.05); and forced expiratory volume at one second as a percent of predicted, 1.19 (1.05-1.34) [14].

Anatomical context of ITM2B

• Removal of most of the APP and BRI2 extracellular domains without affecting the interaction implies that both proteins interact when are expressed on the same cell membrane (cis) rather than on adjacent cells (trans) [1].
• In pathological cases, BRI was detected in dystrophic neurites in senile plaques, around lesions in ischemic cases, in torpedo and glumose changes in the cerebellum, Lewy neurites, ballooned neurons, and neurons generally in hypoxic cases [7].
• Following cleavage, the BRI2-derived carboxyl-terminal peptides are transported via a regulated secretory pathway into secretory vesicles in neuronal cells [3].
• The biosynthesis of the HLA-DR antigens was studied in the B lymphoblastoid cell line BRI 8 [15].
• The heavy chains of the HLA-A and -B antigens were inserted asymmetrically into the rough endoplasmic reticulum of BRI 8 cells as transmembrane polypeptides [4].

Associations of ITM2B with chemical compounds

• Properties of neurotoxic peptides related to the BRI gene [16].
• In the rat model, heparin did not inhibit the uptake of FBD [17].
• A 68 000-Mr protein is a major component of a Nonidet P-40-insoluble fraction of lymphocyte plasma membrane prepared from human B lymphoblastoid cells ( BRI 8) and pig mesenteric lymph nodes [18].
• For instance, why should 2 samples sharing the same BRI but with different ionized calcium and oxalate values have the same likelihood of being obtained from a stone former [19]?
• PURPOSE: The BRI has been shown to discriminate between calcium oxalate stone formers and controls [19].

Physical interactions of ITM2B

• BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production [1].
• The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production [6].

Other interactions of ITM2B

• A specific interaction between BRI2 and APP was unveiled by immunoprecipitation experiments using transfected and non-transfected cells [1].
• Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides [20].
• Only four genes (ITM2B, CHC1L, KIAA0970, and LOC51131), located in the region most frequently deleted in prostate carcinoma, showed a significant difference in expression between normal and neoplastic prostate tissues [11].

Analytical, diagnostic and therapeutic context of ITM2B

• N-terminal sequence analysis of isolated leptomeningeal amyloid fibrils revealed homology to ABri, the peptide originated by a point mutation at the stop codon of gene BRI in familial British dementia [10].
• Three antibodies were raised against sequences of BRI and were used for immunoblotting and immunohistochemistry [7].
• We hypothesized that an elevated BRI at the LT in patients with CF awaiting lung transplantation would be a predictor of wait list mortality [14].
• RESULTS: Simple linear regression analysis showed a significant correlation between portal perfusion index and BRI1 (p < 0.05, r = -0.43) and BRI2 (p = 0.01, r = -0.53) [21].
• Among women who completed the treatment period (valid completers), those of group A showed a progressive decrease in forearm bone density (FBD; measured by dual photon absorptiometry) that reached 1.7% after 12 months [22].

References