Alternative titles; symbols
HGNC Approved Gene Symbol: DSTN
Cytogenetic location: 20p12.1 Genomic coordinates (GRCh38): 20:17,570,075-17,609,919 (from NCBI)
Destrin is an essential actin regulatory protein belonging to the actin-depolymerizing factor (ADF)/cofilin family (see 601442). This family of proteins is responsible for enhancing the turnover rate of actin in vivo.
ADF was first isolated from chick embryo brains as a protein that promoted the disassembly of actin filaments (Bamburg et al., 1980). Hawkins et al. (1993) cloned human ADF from an embryonic brain cDNA library. They found that the deduced 165-amino acid protein is 100% and 95% identical to porcine destrin (Moriyama et al., 1990) chick ADF, respectively.
Hawkins et al. (1993) showed that human destrin expressed in E. coli behaved like native destrin from porcine brain. It bound to G-actin at pH 8, thereby sequestering monomers and preventing polymerization. It did not cosediment with F-actin at this pH, but severed actin filaments in a calcium-insensitive manner. By contrast, at pH values below 7, destrin bound to actin filaments in a highly cooperative manner and at a 1:1 ratio to filament subunits. When the pH was raised to 8.0, the decorated filaments were rapidly severed and depolymerized.
Deloukas et al. (2001) assembled a physical map of human chromosome 20 and annotated 727 genes, one of which was destrin.
Corneal disease-1 (corn1) and corn1(2J) are spontaneous mouse mutants that develop irregular thickening of the corneal epithelium, similar to that observed in human corneal surface disease. These autosomal recessive mutations cause an increase in the rate of proliferation of the corneal epithelial cells. Ikeda et al. (2003) reported that the phenotypes in both mutants are caused by mutations in the destrin gene. By positional cloning, they identified a deletion encompassing the entire coding sequence of the destrin gene in corn1 mice and a point mutation, pro106 to ser (P106S), in corn1(2J) mice. In situ analysis showed that destrin was highly expressed in the corneal epithelium. The corn1 mutations increased the content of filamentous actin in corneal epithelial cells. Ikeda et al. (2003) suggested that there is an in vivo connection between remodeling of the actin cytoskeleton and the control of cell proliferation, at least in the corneal epithelium.
Bamburg, J. R., Harris, H. E., Weeds, A. G. Partial purification and characterization of an actin depolymerizing factor from brain. FEBS Lett. 121: 178-182, 1980. [PubMed: 6893966] [Full Text: https://doi.org/10.1016/0014-5793(80)81292-0]
Deloukas, P., Matthews, L. H., Ashurst, J., Burton, J., Gilbert, J. G. R., Jones, M., Stavrides, G., Almeida, J. P., Babbage, A. K., Bagguley, C. L., Bailey, J., Barlow, K. F., and 115 others. The DNA sequence and comparative analysis of human chromosome 20. Nature 414: 865-871, 2001. [PubMed: 11780052] [Full Text: https://doi.org/10.1038/414865a]
Hawkins, M., Pope, B., Maciver, S. K., Weeds, A. G. Human actin depolymerizing factor mediates a pH-sensitive destruction of actin filaments. Biochemistry 32: 9985-9993, 1993. [PubMed: 8399167] [Full Text: https://doi.org/10.1021/bi00089a014]
Ikeda, S., Cunningham, L. A., Boggess, D., Hawes, N., Hobson, C. D., Sundberg, J. P., Naggert, J. K., Smith, R. S., Nishina, P. M. Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Hum. Molec. Genet. 12: 1029-1036, 2003. Note: Erratum: Hum. Molec. Genet. 12: 1359 only, 2003. [PubMed: 12700171] [Full Text: https://doi.org/10.1093/hmg/ddg112]
Moriyama, K., Nishida, E., Yonezawa, N., Sakai, H., Matsumoto, S., Iida, K., Yahara, I. Destrin, a mammalian actin-depolymerizing protein, is closely related to cofilin: cloning and expression of porcine brain destrin cDNA. J. Biol. Chem. 265: 5768-5773, 1990. [PubMed: 2156828]