The ability of an organism to adapt to its surrounding environment is at the essence of survival. In metazoa, this ability starts at the level of the individual cell, which utilizes a specialized set of cytoskeletal proteins to determine their overall shape and the organization of their intracellular protein complexes and organelles. During embryonic development, the dynamic nature of the actin cytoskeleton is critical for virtually all morphogenic events requiring changes in cell shape, migration, adhesion, and division. The behavior of the actin cytoskeleton is modulated by a myriad of accessory proteins. Shroom3 (Shrm3) is an actin binding protein that regulates neural tube morphogenesis by eliciting changes in cell shape through a myosin II-dependent pathway. The Shroom-related gene SHROOM4 (formerly called KIAA1202) has also been implicated in neural development, as mutations in this gene are associated with human X-linked mental retardation. To better understand the function of Shrm4 in embryonic development, the mouse Shrm4 gene was cloned and its protein product was characterized both in vivo and in vitro. Shrm4 is expressed in a wide range of tissue types during mouse development, including the vascular endothelium of the lung and the polarized epithelium of the neural tube and kidney. In endothelial cells and embryo fibroblasts, endogenous Shrm4 co-distributes with myosin II to a distinct cytoplasmic population of F-actin and ectopic expression of Shrm4 in multiple cell types enhances or induces the formation of this actin-based structure. This localization is mediated, at least in part, by the direct interaction of Shrm4 and F-actin. The actin-binding motif of mShrm4 defines a novel actin-binding element that has not yet been described in other proteins. The results described here suggest that mShrm4 is a regulator of the actin cytoskeleton and may play an important role during vertebrate development, particularly in the developing vasculature.
|School:||University of Pittsburgh|
|School Location:||United States -- Pennsylvania|
|Source:||DAI-B 68/10, Dissertation Abstracts International|
|Keywords:||Actin-binding proteins, Cytoskeletal rearrangements, Myosin II, Shroom protein family, Shroom4, X-linked mental retardation|
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