Disease relevance of SPTBN1

• Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin [1].
• The degradation of alphaII- and betaII-spectrin during apoptosis in cultured human neuroblastoma SH-SY5Y cells was investigated [2].

High impact information on SPTBN1

• Thus, alternative splicing of NF2 may regulate betaII-spectrin binding [1].
• Isoform 1 of schwannomin, in contrast, interacted weakly with betaII-spectrin, presumably because of its strong self-interaction [1].
• Three naturally occurring NF2 missense mutations showed reduced, but not absent, betaII-spectrin binding, suggesting an explanation for the milder phenotypes seen in patients with missense mutations [1].
• We show here that the short C-terminal splice variant of betaII-spectrin (betaIISigma2) is a substrate for phosphorylation [3].
• Simultaneous degradation of alphaII- and betaII-spectrin by caspase 3 (CPP32) in apoptotic cells [2].

Biological context of SPTBN1

• Five human expressed sequence tags indicated the existence of a short splice variant of betaII spectrin [4].
• The schwannomin L46R mutation may result in a complex conformational change that alters folding and denies betaII-spectrin access to an intact binding site in the C-terminal half of schwannomin [5].
• NFs move down the axon with the slow component of axonal transport, together with microtubules, microfilaments, and alphaII/betaII-spectrin (nonerythroid spectrin or fodrin) [6].

Anatomical context of SPTBN1

• As a first step to understanding this interaction, kinetic and equilibrium assays have been used to monitor which regions of beta I and beta II spectrin inhibit the binding of purified 125I-labeled bovine brain spectrin to demyelinated and NaOH-stripped bovine brain membranes [7].
• In rat heart and skeletal muscle, both long and short C-terminal forms of betaII spectrin localized in the region of the Z line [4].
• We postulate that in concert with calpain, caspase rapidly targets critical sites in both alphaII- and betaII-spectrin and thereby initiates a rapid dissolution of the spectrin-actin cortical cytoskeleton with apoptosis [2].

Associations of SPTBN1 with chemical compounds

• Beta II-spectrin (fodrin) and beta I epsilon 2-spectrin (muscle) contain NH2- and COOH-terminal membrane association domains (MAD1 and MAD2) [7].
• Phosphorylation of a Threonine Unique to the Short C-terminal Isoform of betaII-Spectrin Links Regulation of {alpha}-beta Spectrin Interaction to Neuritogenesis [3].

Other interactions of SPTBN1

• Using the yeast two-hybrid system, we identified betaII-spectrin (also known as fodrin) as a schwannomin-binding protein [1].
• Previously, we showed that schwannomin with missense mutations L360P, L535P, and Q538P alters interaction with betaII-spectrin and Hrs [5].
• In the present study we seek to elucidate the relationship between NF-L and betaII-spectrin in vivo [6].

References