Alternative titles; symbols
HGNC Approved Gene Symbol: STMN2
Cytogenetic location: 8q21.13 Genomic coordinates (GRCh38): 8:79,611,117-79,666,158 (from NCBI)
STMN2 is a neuronal growth-associated protein that shares significant amino acid sequence similarity with the phosphoprotein stathmin (STMN1; 151442) (Okazaki et al., 1993).
The rat SCG10 cDNA was cloned by Stein et al. (1988), and Okazaki et al. (1993) isolated most of the mouse gene. The predicted amino acid sequences of SCG10 in the 2 species differ by a single residue (see erratum for Okazaki et al., 1993). The mouse Scgn10 transcription unit spans at least 30 kb, while the stathmin gene is 6 kb long. Both genes have 5 exons. Southern blot analysis indicated that Scgn10 is encoded by a single gene in the mouse that is linked to Il7 in the proximal region of chromosome 3. Okazaki et al. (1993) suggested that in contrast to the more broadly expressed stathmin gene, the neuron-specific SCG10 gene may have evolved by duplication and acquisition of a tissue-specific promoter.
Schoenherr and Anderson (1995) cloned a transcription factor, which they termed neuron-restrictive silencer factor (NRSF; 600571), that repressed transcription of SCG10 by binding to a 24-bp regulatory element, called the neuron-restrictive silencer element (NRSE), located in the distal 5-prime regulatory region of the gene.
Using indexing-based differential display PCR on neuronal precursor cells to study gene expression in Down syndrome (190685), Bahn et al. (2002) found that genes regulated by the REST (600571) transcription factor were selectively repressed. One of these genes, SCG10, was almost undetectable. The REST factor itself was also downregulated by 49% compared to controls. In cell culture, the Down syndrome cells showed a reduction of neurogenesis, as well as decreased neurite length and abnormal changes in neuron morphology. The authors noted that REST-regulated genes play an important part in brain development, plasticity, and synapse formation, and they suggested a link between dysregulation of REST and some of the neurologic deficits seen in Down syndrome.
Using immunohistochemistry, Greka et al. (2003) showed that stathmin-like-2 colocalized with the transient receptor potential cation channel TRPC5 (300334) in cytoplasmic transport vesicles along hippocampal neuronal processes and in the growth cone. In cells transfected with mutant stathmin-like-2, the TRPC5 signal was significantly reduced, and the authors suggested that stathmin-like-2 is required for loading of TRPC5 in the transport vesicles. A dominant-negative form of TRPC5 allowed significantly longer neurites and filopodia to form, indicating that TRPC5 may regulate neuronal growth. Greka et al. (2003) noted that influxes of calcium via voltage-gated channels play a role in neuronal outgrowth and suggested that TRPC5 is a candidate for the regulation of calcium waves.
By yeast 2-hybrid analysis of an embryonic mouse cDNA library, Alves et al. (2010) found that Kbp (KIFBP; 609367) interacted with the microtubule-destabilizing protein Scg10, with tubulin alpha-7 (Tuba3b), and with several kinesins. Coimmunoprecipitation analysis of transfected HEK293 cells and colocalization of Kbp and Scg10 in N1E-115 cells confirmed the interaction between Kbp and Scg10. Kbp did not appear to interact directly with microtubules. Knockdown of Kbp expression in rat PC12 cells inhibited NGF-beta (NGFB; 162030)-induced neurite outgrowth. Alves et al. (2010) concluded that KBP has an indirect role in regulating microtubule dynamics and neurite outgrowth via its interaction with SCG10.
Gross (2012) mapped the STMN2 gene to chromosome 8q21.13 based on an alignment of the STMN2 sequence (GenBank BC006302) with the genomic sequence (GRCh37).
Alves, M. M., Burzynski, G., Delalande, J.-M., Osinga, J., van der Goot, A., Dolga, A. M., de Graaff, E., Brooks, A. S., Metzger, M., Eisel, U. L. M., Shepherd, I., Eggen, B. J. L., Hofstra, R. M. W. KBP interacts with SCG10, linking Goldberg-Shprintzen syndrome to microtubule dynamics and neuronal differentiation. Hum. Molec. Genet. 19: 3642-3651, 2010. [PubMed: 20621975] [Full Text: https://doi.org/10.1093/hmg/ddq280]
Bahn, S., Mimmack, M., Ryan, M., Caldwell, M. A., Jauniaux, E., Starkey, M., Svendsen, C. N., Emson, P. Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down's syndrome: a gene expression study. Lancet 359: 310-315, 2002. [PubMed: 11830198] [Full Text: https://doi.org/10.1016/S0140-6736(02)07497-4]
Greka, A., Navarro, B., Oancea, E., Duggan, A., Clapham, D. E. TRPC5 is a regulator of hippocampal neurite length and growth cone morphology. Nature Neurosci. 6: 837-845, 2003. [PubMed: 12858178] [Full Text: https://doi.org/10.1038/nn1092]
Gross, M. B. Personal Communication. Baltimore, Md. 5/2/2012.
Okazaki, T., Yoshida, B. N., Avraham, K. B., Wang, H., Wuenschell, C. W., Jenkins, N. A., Copeland, N. G., Anderson, D. J., Mori, N. Molecular diversity of the SCG10/stathmin gene family in the mouse. Genomics 18: 360-373, 1993. Note: Erratum: Genomics 21: 298 only, 1994. [PubMed: 8288240] [Full Text: https://doi.org/10.1006/geno.1993.1477]
Schoenherr, C. J., Anderson, D. J. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science 267: 1360-1363, 1995. [PubMed: 7871435] [Full Text: https://doi.org/10.1126/science.7871435]
Stein, R., Mori, N., Matthews, K., Lo, L.-C., Anderson, D. J. The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons. Neuron 1: 463-476, 1988. [PubMed: 3272176] [Full Text: https://doi.org/10.1016/0896-6273(88)90177-8]