The carboxyterminal EF domain of erythroid alpha-spectrin is necessary for optimal spectrin-actin binding (Blood, 2010k, 116(14):2600-2607)

報告日期: 2011/04/26
報告時間: 16:00/16:50
報告學生: 王雅惠 (英文報告)
講評老師: 何中良
附件下載:

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0426-3.pdf

The carboxyterminal EF domain of erythroid α-spectrin is necessary for
optimal spectrin-actin binding
Blood. 2010; 116(14): 2600-2607
 
Speaker:王雅惠
Commentator何中良老師
Time:2011/04/26 pm: 5:00
Space:602 教室
 
Abstract:
The ability of a RBC to maintain its discoid shape, elasticity and deformability in the circulation is attributed to the components of the cell membrane. In cytoplasm, the ternary complex of spectrin, F-actin, and protein 4.1R defines the erythrocyte membrane skeletal network, which governs the stability and elasticity of the membrane. Actin and protein 4.1R bind to calponin homology (CH) domains in the actin-binding domain (ABD) at the N-terminus of the spectrin β-chain. The adjacent end of α-spectrin, called the EF domain, is calmodulin-like, with calcium-dependent and calcium-independent EF hands. However, the function of the EF domain is still unknown. Previous study demonstrated the sph1J/sph1J mouse, which had severe hereditary spherocytosis and unstable red cell membranes due to a mutant α-spectrin that lacks the last 13 amino acids of the EF domain. Therefore, it was suggested that the EF domain is critical for skeletal integrity. In this paper, the authors constructed a minispectrin heterodimer (α_18-21EF_13) containing the actin-binding domain of β-spectrin, the EF domain α-spectrins, and 4 adjacent spectrin repeats in each chain. The results showed that sph1J mutant minispectrin bind far less F-actin than the normal minispectrin in the presence of protein 4.1R. The α-spectrin deletion did not interfere with spectrin heterodimer assembly or 4.1R binding but abolished the binary interaction between spectrin and F-actin. In conclusion, the sph1J mutation is near the 4.1R-actin-binding region at the junctional complex providing evidence that EF domain modulates the function of the ABD and that the C-terminal EF hands (EF34) may bind to the linker that connects the ABD to the first spectrin repeat.
 
References
1.     Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in α-spectrin–deficient red cells (Luanne L. Peters et.al Blood. 2010;115:1804-1814)
2.    Mutations in the murine erythroid _α-spectrin gene alter spectrin mRNA and protein levels and spectrin incorporation into the red blood cell membrane skeleton.Jane E. Barker et.al Blood. 2003;101:325-330