| 1988 |
STMN2 (SCG10) protein is tightly associated with membranes (but is not an integral membrane protein) and accumulates in perinuclear cytoplasm, axons, and growth cones of cultured neurons, as shown by cell fractionation and immunocytochemical localization with an affinity-purified antibody. |
Cell fractionation, immunocytochemistry |
Neuron |
Medium |
3272176
|
| 1990 |
The SCG10 gene contains a constitutive enhancer-like element in the promoter-proximal region and an upstream silencer that preferentially suppresses enhancer activity in nonneuronal cells in an orientation-independent manner, establishing a derepression mechanism for neuron-specific expression. |
Deletion analysis, transfection reporter assays |
Neuron |
High |
2322462
|
| 1992 |
A 21 bp neural-restrictive silencer element (NRSE) in the SCG10 gene binds a sequence-specific factor (NRSBF) present in nonneuronal but not neuronal nuclear extracts; a point mutation abolishing in vitro binding also eliminates in vivo silencing activity. |
Deletion analysis, electrophoretic mobility shift assay (EMSA), point mutagenesis, transfection reporter assay |
Neuron |
High |
1321646
|
| 1997 |
SCG10 binds to microtubules, inhibits their assembly, and can induce microtubule disassembly in vitro; overexpression enhances neurite outgrowth in a stably transfected neuronal cell line, identifying it as a regulator of microtubule instability. |
In vitro microtubule assembly assay, stable cell transfection, neurite outgrowth quantification |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9012855
|
| 1997 |
The N-terminal 34-amino-acid domain of SCG10 is necessary and sufficient for membrane targeting and Golgi localization; two cysteine residues (Cys22 and Cys24) within this domain are sites of palmitoylation, as shown by biosynthetic [3H]palmitic acid labeling. |
Deletion/fusion constructs in PC12 and COS-7 cells, biosynthetic radiolabeling with [3H]palmitic acid, immunofluorescence |
The Journal of biological chemistry |
High |
9030585
|
| 1997 |
SCG10 is phosphorylated in vitro by MAP kinase, cAMP-dependent protein kinase, cGMP-dependent protein kinase, p34cdc2 kinase, DNA-dependent protein kinase, Ca2+/calmodulin kinase II, casein kinase II, and Src tyrosine kinase, but not by casein kinase I or protein kinase C. |
In vitro phosphorylation assay with recombinant protein |
Protein expression and purification |
Medium |
9126608
|
| 1998 |
SCG10 is phosphorylated in vivo at Ser50 and Ser97 by protein kinase A, and at Ser62 and Ser73 by MAP kinase; Ser73 is also a CDK substrate. Non-phosphorylatable mutants show increased microtubule-destabilizing activity while phosphomimetic (Ser→Asp) mutants show decreased activity, demonstrating that phosphorylation negatively regulates SCG10's microtubule-destabilizing function. |
2D gel electrophoresis, mass spectrometry, in vitro kinase assay, site-directed mutagenesis, COS-7 cell transfection microtubule disruption assay |
The Journal of biological chemistry |
High |
9525956
|
| 2000 |
SCG10 localizes by immunoelectron microscopy to the trans-face Golgi complex and growth cone vesicles in developing cortex; palmitoylation of Cys22/Cys24 in the N-terminal domain is required for Golgi sorting and growth cone targeting, as shown by deletion/mutation of the N-terminal domain in transfected PC12 cells and primary neurons. |
Immunoelectron microscopy, subcellular fractionation, transfection of mutant/fusion constructs, immunofluorescence |
The European journal of neuroscience |
High |
10947801
|
| 2001 |
JNK3/SAPKβ directly binds and phosphorylates SCG10 at Ser62 and Ser73, reducing its microtubule-destabilizing activity; endogenous SCG10 shows increased phosphorylation in sympathetic neurons deprived of NGF, a condition that activates JNK. |
In vitro binding assay, in vitro kinase assay, mass spectrometry, phosphorylation in NGF-deprived sympathetic neurons |
FEBS letters |
Medium |
11718727
|
| 2002 |
RGSZ1 directly interacts with SCG10 (confirmed by yeast two-hybrid and direct binding assays) and, upon binding, blocks SCG10's ability to induce microtubule disassembly in vitro. NGF treatment causes both proteins to co-localize at the Golgi in PC12 cells. |
Yeast two-hybrid, direct binding assay, in vitro microtubule polymerization/turbidimetry assay, GFP-tagging and immunofluorescence |
The Journal of biological chemistry |
High |
11882662
|
| 2002 |
RGS6 interacts with SCG10 via its GGL domain binding to SCG10's stathmin domain (yeast two-hybrid and GST pull-down); RGS6 potentiates SCG10-induced microtubule disruption and synergistically enhances NGF-induced PC12 differentiation with SCG10. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, immunofluorescence co-localization, PC12 differentiation assay |
The Journal of biological chemistry |
High |
12140291
|
| 2004 |
EphB stimulation in retinal growth cones causes reduced levels of SCG10, and antibody blockade of SCG10 function mimics EphB-induced changes in microtubule distribution and growth cone pause responses, placing SCG10 downstream of EphB guidance signaling. |
Pharmacological growth cone stimulation, immunofluorescence, antibody blockade functional assay |
The Journal of neuroscience |
Medium |
14985440
|
| 2006 |
JNK1 phosphorylates SCG10 in vivo at Ser62 and Ser73 in developing forebrain (Ser73 phosphorylation is reduced in JNK1-/- cortex); JNK phosphorylation of SCG10 determines axodendritic length, and expression of SCG10-S62A/S73A (non-phosphorylatable) inhibits fluorescent tubulin recovery after photobleaching, linking JNK1-SCG10 phosphorylation to microtubule dynamics. |
Affinity purification of JNK-interacting proteins from brain, in vivo phosphorylation in JNK1-/- mice, FRAP, cerebrocortical neuron cultures with mutant constructs |
The Journal of cell biology |
High |
16618812
|
| 2006 |
SCG10 siRNA knockdown suppresses neurite outgrowth and alters growth cone microtubule morphology toward a more stable state in rat hippocampal neurons; protein transduction of SCG10 stimulates outgrowth and produces more dynamic microtubule morphology. Excess SCG10 causes neurite retraction. |
siRNA knockdown, immunodepletion, protein transduction, immunofluorescence of growth cone microtubules |
Journal of neurobiology |
Medium |
16838365
|
| 2007 |
In contrast to stathmin, SCG10 stabilizes microtubule plus ends (increasing growth rate) while destabilizing minus ends (increasing shortening rate and catastrophe frequency) at steady state in vitro; SCG10 binds along the length of purified microtubules. |
In vitro dynamic instability assay (video microscopy of individual microtubules), microtubule co-sedimentation/pull-down |
Biochemistry |
High |
17311410
|
| 2008 |
SCG10 interacts with chromogranin A (CHGA) and co-localizes with it at the Golgi; siRNA knockdown of SCG10 virtually abolishes regulated secretion of a CHGA reporter, and a palmitoylation-deficient dominant negative SCG10 (C22A/C24A) blocks CHGA-EAP secretion. SCG10 knockdown decreases buoyant density of chromaffin granules. |
Phage display, co-immunoprecipitation, siRNA knockdown, dominant-negative mutant, secretion assay, density gradient fractionation |
Biochemistry |
Medium |
18549247
|
| 2010 |
KBP (Kinesin Binding Protein) physically interacts with SCG10 (yeast two-hybrid, validated biochemically); in zebrafish, epistasis experiments demonstrate a genetic interaction between KBP and SCG10 in vivo, linking this interaction to the neuronal differentiation and microtubule-related defects of Goldberg-Shprintzen syndrome. |
Yeast two-hybrid, biochemical validation, zebrafish epistasis experiments |
Human molecular genetics |
Medium |
20621975
|
| 2011 |
JNK1 phosphorylation of SCG10 governs multipolar-stage exit and radial neuronal migration rate during cortical development; expressing a phosphomimetic SCG10 mutant rescued normal migration in JNK1-/- mouse embryos, placing JNK1-SCG10 phosphorylation as a key negative regulator of cortical neuron migration. |
Jnk1-/- mouse embryos, in utero electroporation of SCG10 phospho-mutants, live imaging of cortical migration |
Nature neuroscience |
High |
21297631
|
| 2011 |
Calmyrin1 (CaMy1) directly and Ca2+-dependently binds SCG10 via its C-terminal domain (residues 99–192) interacting with SCG10's N-terminal domain (residues 1–35); CaMy1 interferes with SCG10's microtubule-polymerization inhibitory activity and inhibits SCG10-mediated neurite outgrowth in NGF-stimulated PC12 cells. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, proximity ligation assay, in vitro microtubule polymerization assay, PC12 neurite outgrowth assay |
Biochimica et biophysica acta |
High |
21215777
|
| 2012 |
SCG10 is an axonal JNK substrate that is rapidly lost from axons distal to injury via JNK-dependent phosphorylation targeting it for degradation; in healthy axons SCG10 undergoes JNK-dependent degradation and is replenished by fast axonal transport. Knockdown of SCG10 accelerates axon fragmentation, while maintaining SCG10 after injury promotes mitochondrial movement and delays degeneration. |
Mouse dorsal root ganglion axotomy model, pharmacological JNK inhibition, shRNA knockdown, lentiviral SCG10 overexpression, live mitochondrial imaging |
Proceedings of the National Academy of Sciences of the United States of America |
High |
23188802
|
| 2013 |
CB1 cannabinoid receptor activation recruits c-Jun N-terminal kinases to phosphorylate SCG10, promoting its rapid degradation in motile axons and microtubule stabilization; this leads to ectopic filopodia formation and altered axon morphology. |
THC exposure in fetal brain, proteomic analysis, pharmacological CB1 receptor manipulation, JNK inhibition, immunofluorescence |
The EMBO journal |
Medium |
24469251
|
| 2013 |
SCG10 directly interacts with the KFFEQ motif of the APP intracellular domain (co-IP, co-localization); SCG10 knockdown reduces α-cleavage products (sAPPα, CTFα) and increases Aβ1-40/1-42, while SCG10 elevation promotes APP accumulation in post-Golgi vesicles and on the cell surface, reducing amyloid plaques in APPswe/PS1dE9 mice. This effect requires palmitoylation-mediated membrane anchoring of SCG10. |
Co-immunoprecipitation, immunofluorescence, siRNA knockdown, overexpression, ELISA (Aβ measurement), in vivo mouse model |
Human molecular genetics |
Medium |
23863461
|
| 2013 |
PAK4 phosphorylates SCG10 at Ser50; phosphorylated SCG10 regulates microtubule dynamics to promote gastric cancer cell migration and invasion in vitro and metastasis in xenograft models. |
In vitro kinase assay, siRNA knockdown, PAK4 inhibitor, invasion/migration assays, xenograft mouse model |
Oncogene |
Medium |
23893240
|
| 2015 |
Spy1 (a Speedy/RINGO family protein) binds SCG10 and mediates its phosphorylation and proteasomal degradation in a partly JNK-dependent manner after sciatic nerve injury; inhibition of Spy1 attenuates SCG10 phosphorylation and delays injury-induced axonal degeneration. |
Co-immunoprecipitation, sciatic nerve injury model, Spy1 inhibition, Western blot for SCG10 levels |
The Journal of biological chemistry |
Medium |
25869138
|
| 2019 |
TDP-43 depletion in human motor neurons causes loss of STMN2 expression due to altered splicing (inclusion of a cryptic exon/premature polyadenylation). STMN2 is necessary for normal axonal outgrowth and regeneration; post-translational stabilization of STMN2 rescues neurite outgrowth and axon regeneration deficits caused by TDP-43 depletion. |
TDP-43 knockdown in iPSC-derived human motor neurons, RNA-seq, RT-PCR, axon regeneration assay, post-translational stabilization rescue |
Nature neuroscience |
High |
30643292
|
| 2021 |
STMN2 modulates microtubule disassembly to disrupt the MT-Smad2/3 complex, facilitating Smad2/3 release, phosphorylation, and nuclear translocation even independent of TGFβ stimulation, thereby enhancing TGFβ signaling and promoting epithelial-mesenchymal transition in hepatocellular carcinoma. |
STMN2 overexpression/knockdown, immunofluorescence, co-immunoprecipitation, in vitro invasion assay, in vivo xenograft |
Cancer letters |
Medium |
33705863
|
| 2022 |
Homozygous loss-of-function Stmn2 mice exhibit neuromuscular junction denervation and fragmentation, muscle atrophy, impaired motor behavior, and neuronal microtubule dynamics imbalance in spinal cord; these phenotypes are rescued by BAC transgenesis of human STMN2, demonstrating that STMN2 is required for motor system maintenance. |
Gene-edited Stmn2 knockout mice, BAC transgenic rescue, NMJ histology, behavioral motor testing, immunofluorescence of microtubules |
Neuron |
High |
35294901
|
| 2023 |
TDP-43 binding to a GU-rich region in STMN2 pre-mRNA sterically blocks recognition of a cryptic 3′ splice site. Targeting dCasRx or antisense oligonucleotides (ASOs) to this region suppressed cryptic splicing, restoring axonal regeneration and stathmin-2-dependent lysosome trafficking in TDP-43-deficient human motor neurons. In mice gene-edited to carry human STMN2 cryptic sequences, intrathecal ASO injection corrected pre-mRNA misprocessing and restored stathmin-2 levels. |
Biochemical TDP-43 binding assays, dCasRx targeting, ASO treatment, iPSC-derived motor neuron axonal regeneration assay, lysosome trafficking assay, humanized mouse model with CSF ASO injection |
Science |
High |
36927019
|
| 2024 |
Stress-induced nuclear TDP-43 condensation (requiring TDP-43 oligomerization and ATP, inhibited by RNA) transiently inactivates TDP-43, causing loss of interaction with protein binding partners and splicing loss-of-function; STMN2 splicing changes are especially prominent and persistent, leading to rapid STMN2 protein depletion early during stress. |
Confocal nanoscanning assay, co-immunoprecipitation, RNA splicing analysis, Western blot for STMN2 protein, ALS-linked TDP-43 mutants |
Cell reports |
Medium |
38941189
|
| 2025 |
STMN2 is primarily degraded by the ubiquitin-proteasome system; its membrane-targeting N-terminal domain promotes fast turnover while its tubulin-binding stathmin-like domain promotes stabilization. Tubulin binds preferentially to soluble (non-membrane-bound) STMN2, reducing its targeting to trans-Golgi network membranes, suggesting STMN2 interconverts between a soluble tubulin-bound form and a membrane-bound tubulin-free form. |
Ubiquitin-proteasome inhibitor treatment, proximity labeling, pull-down assays, imaging in U2OS cells and iPSC-derived neurons, N-terminal domain deletion mutants |
The Journal of cell biology |
High |
41171096
|
| 2025 |
Depletion of SRSF7 (serine/arginine-rich splicing factor 7) in human iPSC-derived neurons decreases STMN2 abundance (but not TDP-43) and impairs axonal regeneration; this phenotype is rescued by exogenous STMN2, placing SRSF7 upstream of STMN2 in a pathway linking C9ORF72 poly-PR toxicity to axonal repair defects. |
SRSF7 siRNA knockdown in iPSC-derived neurons, STMN2 rescue experiment, axonal regeneration assay, global phospho-proteomics |
Acta neuropathologica communications |
Medium |
40140908
|
| 2024 |
STMN2 overexpression restores axonal growth defects in SMA patient iPSC-derived motor neurons; intracerebroventricular AAV9-Stmn2 delivery in SMA mice improves survival, motor function, and neuromuscular junction pathology. |
iPSC-derived motor neuron overexpression assay, AAV9 in vivo delivery in SMA mice, behavioral and histological assessment |
Cellular and molecular life sciences |
Medium |
39725771
|
| 2025 |
In zebrafish double stmn2a/stmn2b knockout larvae, loss of STMN2 impairs motor function, increases orphaned NMJs, reduces miniature endplate current amplitude, and impairs ventral root axon regrowth after transection, demonstrating STMN2 is required for NMJ assembly and axon regeneration but not motor axon development. |
CRISPR/Cas9 double knockout zebrafish, behavioral motor assay, NMJ immunohistochemistry, electrophysiology (mEPCs), axon transection/regeneration assay |
bioRxivpreprint |
Medium |
bio_10.1101_2025.10.24.684380
|
| 2006 |
STMN2 is a direct transcriptional target of β-catenin/TCF signaling; chromatin immunoprecipitation and promoter mapping identified a critical TCF binding site at -1713 of the STMN2 promoter, and siRNA knockdown of STMN2 abolished anchorage-independent growth in β-catenin/TCF-activated hepatoma cells. |
Promoter deletion, ChIP assay, transient transfection, siRNA knockdown, soft agar colony assay |
Biochemical and biophysical research communications |
Medium |
16712787
|
| 2004 |
Protocadherin-γ-b1 (and other Pcdhγ-b subfamily isoforms) interact with SCG10 as a cytoplasmic binding partner, and SCG10 and Pcdhγ-b1 are found together in neuronal growth cones. |
Yeast two-hybrid, co-localization in growth cones |
FEBS letters |
Low |
15581637
|
| 2008 |
BRI3 binds SCG10 (GST pull-down, co-IP) and blocks SCG10's ability to induce microtubule disassembly in vitro; co-expression of BRI3 attenuates SCG10-mediated neurite outgrowth in NGF-stimulated PC12 cells. |
Yeast two-hybrid, GST pull-down, co-immunoprecipitation, turbidimetric microtubule assay, PC12 neurite outgrowth assay |
BMB reports |
Medium |
18452648
|