Disease relevance of Stmn2

• The SCG10-related gene family in the developing rat retina: persistent expression of SCLIP and stathmin in mature ganglion cell layer [1].
• Administration of CPP 1 hr before tetanus completely blocked LTP induction and the increase of SCG10 mRNA levels [2].
• We describe features of the regulation of a neural-specific gene, SCG10, which is induced by nerve growth factor (NGF) during the neuronal differentiation of the rat pheochromocytoma cell line PC12 [3].
• To achieve neuron-targeted gene transfer, we have produced an adenovirus carrying the reporter lacZ gene driven by the SCG10 minimum promoter containing the neural-restrictive silencer element (NRSE), which element selectively represses the transcription of genes in non-neuronal cells [4].

High impact information on Stmn2

• SCG10 is a growth-associated protein that is expressed early in the development of neuronal derivatives of the neural crest [5].
• A cell type-preferred silencer element that controls the neural-specific expression of the SCG10 gene [5].
• Like other neural-specific genes, SCG10 contains multiple transcription initiation sites [5].
• We describe here the isolation of the SCG10 chromosomal gene and the identification of regulatory regions that control its expression [5].
• The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons [6].

Biological context of Stmn2

• Identification of upregulated SCG10 mRNA expression associated with late-phase long-term potentiation in the rat hippocampal Schaffer-CA1 pathway in vivo [2].
• By screening a subtracted cDNA library that is enriched in upregulated transcripts in rat hippocampus 3 hr after Schaffer-CA1 LTP induction in vivo, we identified a neural growth-associated protein SCG10 (superior cervical ganglia clone 10) gene [2].
• We investigated the specific role of the two cAMP-dependent protein kinase (PKA) phosphorylation sites in SCG10 [7].
• Perforant path lesion induces up-regulation of stathmin messenger RNA, but not SCG10 messenger RNA, in the adult rat hippocampus [8].
• It was recently found that SCG10 shares an amino acid sequence similarity with a phosphoprotein named stathmin or p19 of which phosphorylation is induced by nerve growth factor and vasoactive intestinal peptide in PC12 cells and striatal neurons, respectively [9].

Anatomical context of Stmn2

• In situ hybridization revealed that GAP-43 and all of the SCG10-related family mRNAs were present in the retinal ganglion cells (RGCs) at all stages of retinal development, and that stathmin mRNA was present in mitotic neuroblastic cells [1].
• Cross-hybridizing mRNAs and antigenically related proteins are found in several nonneuronal cell lines that do not express SCG10 [6].
• These results suggest that SCG10 may play a role in the maintenance of synaptic plasticity through a transient regulation of microtubule dynamics, which facilitates the structural remodeling of the presynaptic element during the consolidation period [10].
• Previously, we found the expression of neuronal growth associated protein SCG10, which is involved in neurite outgrowth and neural regeneration, was up-regulated by LTP induction in the rat hippocampal Schaffer-collateral CA1 pathway [10].
• Furthermore, RB3 mRNA is undetectable in PC12 cells, whereas SCG10 mRNA increases after treatment with nerve growth factor, inducing neuronal differentiation [11].

Associations of Stmn2 with chemical compounds

• In particular, compared to the two other phosphorylated forms, SCG10 phosphorylated at S50 had a significantly smaller dissociation constant for the binding of the first tubulin heterodimer and larger association and dissociation rate constants for the binding of the second heterodimer [7].
• Disassembly of labile microtubules by nocodazole caused a dispersal of the SCG10 staining into punctate structures, indicating that its subcellular localization is microtubule-dependent [12].
• The proteins were like the full length SCG10 substrate for serine/threonine protein kinases, including MAP kinase, PKA, and p34cdc2 kinase [13].
• Activators of PKC such as phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl 2-acetyl glycerol mimicked the stimulatory effect of NGF and bFGF on SCG10 mRNA levels [14].
• NGF, FGF, and, to a lesser extent, phorbol esters induced SCG10, whereas EGF and dibutyryl cAMP did not [3].

Enzymatic interactions of Stmn2

• c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10 [15].

Other interactions of Stmn2

• At a regional level, SCG10 and SCLIP appear generally distributed similarly except in a few areas [16].
• In addition, we systemically injected the competitive NMDA receptor antagonist d,l-3[(+/-)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (CPP) to determine whether the alteration of SCG10 expression depends on NMDA receptor activation or tetanus alone [2].
• In the olfactory bulb of postnatal and adult rats, a moderate to strong SCG10 immunoreactivity was present in the olfactory nerve layer, whereas no labeling was detected in the glomerular layer [17].
• Effect of nerve growth factor and fibroblast growth factor on SCG10 and c-fos expression and neurite outgrowth in protein kinase C-depleted PC12 cells [14].
• The age-related loss of DAT and TH mRNA expressions was accompanied by diminished expression of mRNA for a neuronal growth-associated protein GAP-43, but not for SCG10 or alpha 1-tubulin [18].

Analytical, diagnostic and therapeutic context of Stmn2

• The real-time RT-PCR showed that both SCG10 mRNA 1 and 2 kb forms were increased at the 3 h, but not at 1 or 24 h [10].
• Here we studied the temporal expression pattern of SCG10 mRNA after LTP induction using permanently implanted electrodes in the same CA1 pathway [10].
• The semiquantitative reverse transcription-PCR and Northern blot experiments confirmed that SCG10 mRNA levels were elevated in tetanized rat hippocampi compared with those of sham controls that received only low-frequency stimulation [2].
• Surface plasmon resonance studies revealed that the phosphorylation of SCG10 at these sites reduced the tubulin heterodimer binding, mainly due to a reduced rate of association [7].
• Thus, in both PNS and CNS neurons, the transcription of SCG10, CAP-23, and GAP-43 mRNAs is coregulated following axotomy and during regeneration [19].

References