Dematin

Definition:

Membrane-cytoskeleton-associated protein with F-actin-binding activity that induces F-actin bundles formation and stabilization. Its F-actin-bundling activity is reversibly regulated upon its phosphorylation by the cAMP-dependent protein kinase A (PKA). Binds to the erythrocyte membrane glucose transporter-1 SLC2A1/GLUT1, and hence stabilizes and attaches the spectrin-actin network to the erythrocytic plasma membrane. Plays a role in maintaining the functional integrity of PKA-activated erythrocyte shape and the membrane mechanical properties. Also plays a role as a modulator of actin dynamics in fibroblasts; acts as a negative regulator of the RhoA activation pathway. In platelets, functions as a regulator of internal calcium mobilization across the dense tubular system that affects platelet granule secretion pathways and aggregation. Also required for the formation of a diverse set of cell protrusions, such as filopodia and lamellipodia, necessary for platelet cell spreading, motility and migration. Acts as a tumor suppressor and inhibits malignant cell transformation.

References:

[1]. Lin Chen, et al. Dematin exhibits a natively unfolded core domain and an independently folded headpiece domain. Protein Sci. 2009 Mar;18(3):629-36. [Content Brief]

[2]. Lin Chen, et al. The allosteric mechanism induced by protein kinase A (PKA) phosphorylation of dematin (band 4.9). J Biol Chem. 2013 Mar 22;288(12):8313-8320. [Content Brief]

[3]. M Lutchman, et al. Loss of heterozygosity on 8p in prostate cancer implicates a role for dematin in tumor progression. Cancer Genet Cytogenet. 1999 Nov;115(1):65-9. [Content Brief]

[4]. Ichiro Koshino, et al. Identification of a novel role for dematin in regulating red cell membrane function by modulating spectrin-actin interaction. J Biol Chem. 2012 Oct 12;287(42):35244-35250. [Content Brief]

[5]. Mohini Lutchman, et al. Dematin interacts with the Ras-guanine nucleotide exchange factor Ras-GRF2 and modulates mitogen-activated protein kinase pathways. Eur J Biochem. 2002 Jan;269(2):638-49. [Content Brief]

[6]. Anwar A Khan, et al. Dematin and adducin provide a novel link between the spectrin cytoskeleton and human erythrocyte membrane by directly interacting with glucose transporter-1. J Biol Chem. 2008 May 23;283(21):14600-9. [Content Brief]

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