Cell organization, growth, and neural and cardiac development require αII-spectrin

被引:63
作者
Stankewich, Michael C. [1 ]
Cianci, Carol D. [1 ]
Stabach, Paul R. [1 ]
Ji, Lan [1 ]
Nath, Anjali [1 ]
Morrow, Jon S. [1 ]
机构
[1] Yale Univ, Dept Pathol, Sch Med, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
Ankyrin; Neuroepithelial cell; Myocardium; Axons; Ventricular zone; Actin cytoskeleton; Cell growth; Development; Exon trap; ATAXIA TYPE 5; BETA-SPECTRIN; ERYTHROCYTE SPECTRIN; MEMBRANE SKELETON; SH3; DOMAIN; ANKYRIN; PROTEIN; CALPAIN; BRAIN; ELF;
D O I
10.1242/jcs.080374
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Spectrin alpha 2 (alpha II-spectrin) is a scaffolding protein encoded by the Spna2 gene and constitutively expressed in most tissues. Exon trapping of Spna2 in C57BL/6 mice allowed targeted disruption of alpha II-spectrin. Heterozygous animals displayed no phenotype by 2 years of age. Homozygous deletion of Spna2 was embryonic lethal at embryonic day 12.5 to 16.5 with retarded intrauterine growth, and craniofacial, neural tube and cardiac anomalies. The loss of alpha II-spectrin did not alter the levels of alpha I- or beta I-spectrin, or the transcriptional levels of any beta-spectrin or any ankyrin, but secondarily reduced by about 80% the steady state protein levels of beta II- and beta III-spectrin. Residual beta II- and beta III-spectrin and ankyrins B and G were concentrated at the apical membrane of bronchial and renal epithelial cells, without impacting cell morphology. Neuroepithelial cells in the developing brain were more concentrated and more proliferative in the ventricular zone than normal; axon formation was also impaired. Embryonic fibroblasts cultured on fibronectin from E14.5 (Spna2(-/-)) animals displayed impaired growth and spreading, a spiky morphology, and sparse lamellipodia without cortical actin. These data indicate that the spectrin-ankyrin scaffold is crucial in vertebrates for cell spreading, tissue patterning and organ development, particularly in the developing brain and heart, but is not required for cell viability.
引用
收藏
页码:3956 / 3966
页数:11
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