Disease relevance of Spnb2

• Exclusion of two candidate genes, Spnb-2 and Dcd, for the wobbler spinal muscular atrophy gene on proximal mouse chromosome 11 [1].
• Serum Ab to the amino-terminal fragment of beta-fodrin was frequently detected in SS patients compared with rheumatic disease patients without SS or healthy controls (70 vs 12 or 4%; p < 0.00001) [2].
• In contrast, intact beta-fodrin was detected primarily at the apical membrane of epithelia, and the amino-terminal fragment was scarcely detected in control patients with chronic graft-vs-host disease [2].
• Autoantibodies to the amino-terminal fragment of beta-fodrin expressed in glandular epithelial cells in patients with Sjögren's syndrome [2].
• Calcium activated proteolysis of brain spectrin produces characteristic breakdown products (BDPs), the concentrations of which increase markedly in many instances of brain pathology [3].

High impact information on Spnb2

• We also show that brain spectrin, a membrane-cytoskeleton linker protein, binds only to N-CAM180 [4].
• Brain spectrin(240/235) is found in neuronal axons, but not dendrites, when immunohistochemistry is performed with antibody raised against brain spectrin isolated from enriched synaptic/axonal membranes [5].
• Amino acid sequence comparison between erythroid and murine brain spectrin (Spnb-2, chromosome 11) shows 67% identity throughout repeats 16 and 17 and complete divergence in domain III, which is associated with the alpha/beta subunit dimerization and phosphorylation [6].
• In the CNS, three isoforms of brain spectrin are known to exist: a cellular and dendritic isoform, (240/235E), related to neurons and glia; a cellular and axonal isoform, (240/235), related to neurons; and an isoform specific for astrocytes, (240/235A) [7].
• We also demonstrate that amelin, like synapsin I, can bind brain spectrin on nitrocellulose paper [8].

Biological context of Spnb2

• Full genomic structural analyses reveal that elf-3 is composed of 31 exons spanning approximately 67 kb, and confirm that elf and mouse brain beta-G-spectrin share multiple exons, with a complex form of exon/intron usage [9].
• The complete amino acid sequence for brain beta spectrin (beta fodrin): relationship to globin sequences [10].
• Using subtractive screening of cDNA libraries from early embryonic mouse livers (post-coital days 10, 11, and 12), we have isolated elf1 (embryonic liver fodrin 1), a differentially expressed beta-spectrin or fodrin (betaSpIIsigmaI) [11].
• These findings suggest that cleavage and altered distribution of beta-fodrin in glandular epithelial cells may induce impaired secretory function and perpetuate an autoimmune response to beta-fodrin, leading to autoantibody production and glandular destruction in SS [2].
• DNA sequence analysis established that the genomic fragment encoded beta-fodrin, the nonerythroid form of beta-spectrin, by correlation to a known amino acid sequence of human brain beta-fodrin [12].

Anatomical context of Spnb2

• The differential expression, tissue localization, and functional studies demonstrate the importance of elf3 in modulating interactions between various components of the cytoskeleton proteins controlling liver and bile duct development [13].
• Antisense studies utilizing cultured liver explants show a vital role of elf3 in hepatocyte differentiation and intrahepatic bile duct formation [13].
• These studies suggest that elf1 may play a role in the emergence of hepatocyte polarity during liver development [11].
• With the aid of two monospecific antibodies raised in rabbits (antimouse erythrocyte spectrin and antimouse brain spectrin), the presence of a spectrin-like protein was demonstrated in mouse adrenal tumor (Y-1) cells [14].
• A single-copy DNA fragment of the beta-fodrin genomic clone was used to screen a lymphoid cell cDNA library and two recombinants were isolated [12].

Associations of Spnb2 with chemical compounds

• Immunofluorescence obtained using antibodies against alphaI SigmaI/++betaI SigmaI spectrin and Abl tyrosine kinase but not against alphaII/betaII spectrin colocalized with the overexpressed green fluorescent protein-SH3-binding protein [15].
• Brain spectrin (240/235) immunoreactivity decreased with increasing protein crosslinking and was dependent on glutaraldehyde concentration and post-fixation period [16].
• Quantitative cryosection immunoassay and immunocytochemical localization confirmed the aldehyde sensitivity of brain spectrin (240/235) [16].
• Binding affinity to [D-Ala2,D-Leu5]enkephalin (DADLE) or ethylketocyclazocine (EKC), the levels of plasma beta-endorphin, and the anatomical location and quantity of Met- and Leu-enkephalin and cytoskeletal components (i.e. tubulin, actin, brain spectrin (240/235) were similar in NTX and control tumor-bearing animals [17].
• Expression of another five genes was increased in W/W(V) mice: ADA (adenosine deaminase), MDH1 (malate dehydrogenase), RPL-8 (ribosomal protein L8), SPTB2 (spectrin, nonerythroid, beta subunit), and p6-5 (encoding phosphorylcholine [PC] T-cell suppressor factor [TsF]) [18].

Regulatory relationships of Spnb2

• In the present study, spectrin was localized in the mouse brain by indirect immunofluorescence using an antibody to erythrocyte spectrin that cross-reacts specifically with the alpha and beta subunits of brain spectrin [19].

Other interactions of Spnb2

• Although the N-terminal and central rod regions of dystrophin share structural homologies with spectrin, the 230-kDa protein represents neither of the presently described forms of brain spectrin by a variety of criteria (molecular weight, cerebellar localisation, and developmental regulation) and is distinct from the product of the dystrophin gene [20].
• The distribution of two isoforms of spectrin in the adult mouse heart was investigated by Western blotting and immunocytochemistry by use of monospecific antibodies to erythrocyte spectrin and nonerythroid brain spectrin (240/235) [21].
• The distribution of NF200 and brain spectrin immunoreactivity suggested that efferent innervation of OHCs is present at birth in the rat, and confirms previous studies showing the early efferent innervation of the OHCs of the mouse and the rat at birth, and the time lag between the appearance of the two spectrin isoforms during development [22].

Analytical, diagnostic and therapeutic context of Spnb2

• Northern blot analysis utilizing an elf3 3'-UTR probe demonstrates an abundant 9.0-kb transcript in brain, liver, and heart tissues [13].
• In situ hybridization studies demonstrate elf1 expression initially in day 10 embryonic heart tissue, then in day 11-11.5 hepatic tissue [11].
• Indirect immunofluorescence of mouse brain tissue with anti-brain spectrin-like protein IgG or anti-erythrocyte spectrin IgG indicated that the distribution of brain spectrin-like protein was normal in sph/sph brain [23].
• Brain spectrin-like protein, a nonerythroid spectrin analogue, is antigenically, morphologically and functionally related to erythrocyte spectrin, but appears by peptide mapping analysis to be a distinct gene product [23].
• Electron microscopy of immunogold-labelled cryosections reveals statistically significant clustering of gold particles near the Z-disc, within and close to the edge of myofibrils. betaII-spectrin and ankyrin-R and G are both known to occupy this region [24].

References