HGNC Approved Gene Symbol: DBN1
Cytogenetic location: 5q35.3 Genomic coordinates (GRCh38) : 5:177,456,610-177,473,634 (from NCBI)
Drebrins are actin-binding proteins that are developmentally regulated in the process of neuronal growth and aid in dendritic spine formation (Shim and Lubec, 2002).
Shirao et al. (1992) cloned the rat drebrin A gene.
Toda et al. (1993) isolated a full-length cDNA clone of human drebrin E by screening a cDNA library constructed from fetal human brain. The deduced 649-amino acid protein shows 88% homology with rat drebrin A, except for an internal 138-nucleotide sequence. There are 3 drebrin isoforms: 2 embryonic types, E1 and E2, and an adult type, A, that are generated by alternative RNA splicing from a single drebrin gene in the chicken brain.
Jin et al. (2002) cloned and characterized a truncated form of mouse drebrin A, termed s-drebrin A, which is generated by alternative splicing of the Dbn1 gene. Expression of s-drebrin A is brain-specific and increases in parallel with drebrin A during brain maturation.
Shirao et al. (1992) found that transient expression of rat drebrin A in fibroblasts induced the formation of highly branched neurite-like cell processes in these nonneuronal cells. The findings suggested a role for drebrin A in neurite outgrowth.
Hayashi and Shirao (1999) found that drebrin colocalized with actin filaments at dendritic spines in cultured rat cerebral cortical neurons. Overexpression of drebrin in these cells resulted in the accumulation of drebrin at the spines and the development of longer postsynaptic spines.
Jin et al. (2002) demonstrated that overexpression of s-drebrin A in mouse fibroblasts showed that the protein was associated with actin filaments and with changes in actin cytoskeleton organization. Jin et al. (2002) suggested that s-drebrin A has a role in spine morphogenesis.
Role in Alzheimer Disease
Drebrin is located in the postsynaptic terminals of adult brain and is thought to play a role in synaptic plasticity. Harigaya et al. (1996) found a significant decrease in both drebrin A and drebrin E in the hippocampus of patients with Alzheimer disease (AD; 104300) compared to controls. Presynaptic protein markers did not significantly differ. The authors concluded that the postsynaptic decrease in drebrin may be a sensitive marker of synaptic damage in AD. Hatanpaa et al. (1999) found decreased levels of drebrin in the cerebral cortex of individuals with normal aging. Alzheimer disease was associated with an additional 81% decrease in drebrin levels. The findings suggested that disturbed plasticity may contribute to cognitive dysfunction in both aging and AD.
Shim and Lubec (2002) examined drebrin distribution in brains from 8 patients with Down syndrome (DS; 190685), 9 patients with AD, and 9 controls. Drebrin (125 kD) expression was significantly decreased in the temporal and frontal cortex of both DS and AD patients compared to controls. Shim and Lubec (2002) suggested that decreased drebrin in DS and AD may represent loss of spine plasticity and impaired dendritic arborization, which may underlie cognitive dysfunction.
By spot blot hybridization using flow-sorted human chromosomes, Toda et al. (1993) determined that the human drebrin gene is located on chromosome 5. By interspecific backcross analysis, Jin et al. (2002) mapped the mouse Dbn1 gene to chromosome 13.
In a transgenic mouse model of AD with a mutation in the amyloid precursor protein (APP; 104760), Calon et al. (2004) found an age-related significant decrease in postsynaptic drebrin (62% decrease at 22 months of age) compared to controls. In the transgenic mice, dietary depletion of docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, resulted in a further decrease in drebrin levels and an increase in the levels of caspase-cleaved actin ('fractin'), a marker of dendritic spine damage. Further studies showed that DHA restriction led to a 95% decrease in the p85-alpha subunit (PIK3R1; 171833) of phosphatidylinositol 3-kinase (PI3-kinase) in the mouse cerebral cortex. Treatment with DHA protected against the changes. Since DHA is a positive regulator of PI3-kinase (Akbar and Kim, 2002), which prevents caspase activation, DHA may indirectly decrease dendritic spine damage induced by caspase. The findings showed that genetic and environmental (dietary) risk factors for AD can act synergistically to reduce synaptic proteins that are critical for cognition.
Akbar, M., Kim, H. Y. Protective effects of docosahexaenoic acid in staurosporine-induced apoptosis: involvement of phosphatidylinositol-3 kinase pathway. J. Neurochem. 82: 655-665, 2002. [PubMed: 12153489] [Full Text: https://doi.org/10.1046/j.1471-4159.2002.01015.x]
Calon, F., Lim, G. P., Yang, F., Morihara, T., Teter, B., Ubeda, O., Rostaing, P., Triller, A., Salem, N., Jr., Ashe, K. H., Frautschy, S. A., Cole, G. M. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 43: 633-645, 2004. [PubMed: 15339646] [Full Text: https://doi.org/10.1016/j.neuron.2004.08.013]
Harigaya, Y., Shoji, M., Shirao, T., Hirai, S. Disappearance of actin-binding protein, drebrin, from hippocampal synapses in Alzheimer's disease. J. Neurosci. Res. 43: 87-92, 1996. [PubMed: 8838578] [Full Text: https://doi.org/10.1002/jnr.490430111]
Hatanpaa, K., Isaacs, K. R., Shirao, T., Brady, D. R., Rapoport, S. I. Loss of proteins regulating synaptic plasticity in normal aging of the brain and in Alzheimer disease. J. Neuropath. Exp. Neurol. 58: 637-643, 1999. [PubMed: 10374754] [Full Text: https://doi.org/10.1097/00005072-199906000-00008]
Hayashi, K., Shirao, T. Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons. J. Neurosci. 19: 3918-3925, 1999. [PubMed: 10234022] [Full Text: https://doi.org/10.1523/JNEUROSCI.19-10-03918.1999]
Jin, M., Tanaka, S., Sekino, Y., Ren, Y., Yamazaki, H., Kawai-Hirai, R., Kojima, N., Shirao, T. A novel, brain-specific mouse drebrin: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization. Genomics 79: 686-692, 2002. [PubMed: 11991718] [Full Text: https://doi.org/10.1006/geno.2002.6764]
Shim, K. S., Lubec, G. Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer's disease and Down syndrome. Neurosci. Lett. 324: 209-212, 2002. [PubMed: 12009525] [Full Text: https://doi.org/10.1016/s0304-3940(02)00210-0]
Shirao, T., Kojima, N., Obata, K. Cloning of drebrin A and induction of neurite-like processes in drebrin-transfected cells. Neuroreport 3: 109-112, 1992. Note: Erratum: Neuroreport 3: 285 only, 1992. [PubMed: 1611026] [Full Text: https://doi.org/10.1097/00001756-199201000-00029]
Toda, M., Shirao, T., Minoshima, S., Shimizu, N., Toya, S., Uyemura, K. Molecular cloning of cDNA encoding human drebrin E and chromosomal mapping of its gene. Biochem. Biophys. Res. Commun. 196: 468-472, 1993. [PubMed: 8216329] [Full Text: https://doi.org/10.1006/bbrc.1993.2273]