Disease relevance of STMN2

• STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells [1].
• As a first step to examine the biochemical properties of SCG10, the protein was expressed in Escherichia coli and purified to apparent homogeneity [2].
• Olf/EBF proteins are expressed in neuroblastoma cells: potential regulators of the Chromogranin A and SCG10 promoters [3].
• In addition to its known binding to tubulin dimers, SCG10 binds also to purified microtubules in growth cones of dorsal root ganglion neurons in culture [4].

Psychiatry related information on STMN2

• SCG10, a neuron-specific growth-associated protein in Alzheimer's disease [5].

High impact information on STMN2

• Our results indicate that TRPC5 channel subunits interact with the growth cone-enriched protein stathmin 2, are packaged into vesicles and are carried to newly forming growth cones and synapses [6].
• JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic length [7].
• SCG10-S73 phosphorylation is significantly decreased in JNK1-/- cortex, indicating that JNK1 phosphorylates SCG10 in developing forebrain [7].
• These data suggest that JNK1 is responsible for regulation of SCG10 depolymerizing activity and neurite elongation during brain development [7].
• The NGF induction of SCG10 mRNA was mimicked only by activated Src and Ras and was blocked by p21N17 Ras, while the induction of Thy-1 mRNA was mimicked only by activated Src and was not blocked by p21N17 Ras [8].

Biological context of STMN2

• The deduced amino acid sequence of human SCG10 was 69% identical to stathmin, another nGAP [5].
• REST functioned as a transcriptional repressor when REST binding motifs derived from the genes encoding synapsin I, SCG10, alpha1-glycine receptor, the beta2-subunit of the neuronal nicotinic acetylcholine receptor, and the m4-subunit of the muscarinic acetylcholine receptor were present in the promoter region [9].
• Its inhibition by RNA interference resulted in increased axonal branching, revealing a novel biological role for SCLIP, distinct from SCG10 whose down-regulation in the same conditions promoted growth cone expansion [10].
• Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence [11].
• These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone [11].

Anatomical context of STMN2

• Here, we report STMN2, a gene implicated in the regulation of microtubule dynamics, as a novel target of beta-catenin-mediated transcription [1].
• STMN2 was up-regulated in hepatoma and cirrhotic liver tissues compared to normal liver and also in cell lines where beta-catenin/TCF is constitutively activated [1].
• RGS6 potentiated the ability of SCG10 to disrupt microtubule organization in PC12 and COS-7 cells [12].
• Previously, we employed the yeast two-hybrid system and identified the microtubule-destabilizing protein, superior cervical ganglia neural-specific 10 protein (SCG10), as a potential effector protein of RGSZ1 [13].
• We investigated the functional role of SCG10 in neurite outgrowth using rat hippocampal primary cultured neurons [14].

Associations of STMN2 with chemical compounds

• On the other hand, the protein transduction of SCG10 using a polyarginine tag stimulated neurite outgrowth [14].
• The protein was not a substrate for casein kinase I and protein kinase C. SCG10 was phosphorylated by src tyrosine kinase, which demonstrates that the protein can be phosphorylated in vitro on a tyrosine residue [2].
• The main structural feature distinguishing the two proteins is that SCG10 contains an NH2-terminal extension of 34 amino acids [15].
• Calpain inhibitor MDL-28170, but not caspase inhibitors, blocked a significant decrease in SCG10 protein levels [16].
• Site-specific phosphorylation of SCG10 in neuronal plasticity: role of Ser73 phosphorylation by N-methyl D-aspartic acid receptor activation in rat hippocampus [17].

Physical interactions of STMN2

• This suggests that SCG10 is more potent to destabilize microtubules than MAP1B to rescue them [4].

Regulatory relationships of STMN2

• Using northern blot and in situ hybridization, we revealed that: (i) silencing retinal activity with tetrodotoxin eye injections dynamically reduced the expression of SCG10 mRNA and (ii) it was enhanced by BDNF in VC and LGN of kittens but not adult cats [18].
• Conversely, Mash1 induces neuronal differentiation characterized by the expression of generic neuronal genes SCG10, Hu and NF160; however, only a subpopulation of these neurons also displays an autonomic, noradrenergic phenotype [19].

Other interactions of STMN2

• By in situ hybridization, both SCG10 and stathmin mRNAs were detected in selected neuronal populations in aged human brains [5].
• Quantitative analysis by RNase protection revealed that levels of neither SCG10 nor stathmin mRNAs were significantly altered in AD [5].
• SCLIP, like SCG10, is present from the earliest stages of hippocampal neuron differentiation in culture at vesicle-like structures following dynamic microtubules [10].
• REST-dependent structures as synapsin I, brain derived neurotrophic factor BDNF and neuronal growth-associated protein SCG10 were determined at the protein level using immunoblotting [20].
• EGF increased the levels of three neurofilament proteins and the mRNA level of two late response genes (SCG10 and 63) known to be induced by NGF [21].

Analytical, diagnostic and therapeutic context of STMN2

• Using an SCG10-specific antibody, Western blot analysis did not reveal any quantitative changes of SCG10 in AD [5].
• Using immunoelectron microscopy, we show that in the developing cortex of mice, SCG10 is specifically localized to the trans face Golgi complex and apparently associated with vesicular structures in putative growth cones [22].
• In a double-blind double-placebo study 10 asthmatics exercised on a treadmill after treatment for 1 week with placebo, or ketotifen 1 mg twice daily, or SCG 10 mg four times daily [23].

References