Launay Sophie, Brown Geoffrey, Machesky Laura M
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Cell Motil Cytoskeleton. 2003 Apr;54(4):274-85. doi: 10.1002/cm.10101.
The Wiskott-Aldrich Syndrome (WAS) is a disease associated with mutations in the WAS gene and characterised by developmental defects in haematopoietic cells such as myeloid cells. The Wiskott-Aldrich Syndrome protein (WASP)-family includes Scar1 and WASP, which are key regulators of actin reorganization in motile cells. To understand the roles of Scar1 and WASP in myeloid cells and their cytoskeletal control in haematopoietic tissues, we have explored their expression during differentiation of the promyeloid cell line HL-60. Undifferentiated HL-60 cells expressed Scar1 and WASP, and differentiation to neutrophils, induced by retinoic acid or non-retinoid agent treatments, led to a decrease in the level of expression of Scar1, whereas WASP expression was unaffected. Differentiation to monocytes/macrophages, induced by phorbol ester treatment, resulted in a decreased expression of both proteins in the adherent mature cells. Vitamin D(3) treatment or cytochalasin D in combination with PMA treatment did not affect WASP expression suggesting that adhesion and cytoskeletal integrity were both essential to regulate WASP expression. Scar1 expression was regulated by differentiation, adhesion, and cytoskeletal integrity. Recently, WASP was found to colocalize with actin in the podosomes. In contrast, we show here that Scar1 did not localize with the podosomes in mature monocytes/macrophages. These observations show for the first time that modulation of Scar1 and WASP expression is a component of the differentiation program of myeloid precursors and indicate that WASP and Scar1 have different roles in mature myeloid cells.
威斯科特-奥尔德里奇综合征（WAS）是一种与WAS基因突变相关的疾病，其特征是造血细胞如髓细胞出现发育缺陷。威斯科特-奥尔德里奇综合征蛋白（WASP）家族包括Scar1和WASP，它们是运动细胞中肌动蛋白重组的关键调节因子。为了了解Scar1和WASP在髓细胞中的作用及其在造血组织中的细胞骨架控制，我们研究了它们在早幼粒细胞系HL-60分化过程中的表达。未分化的HL-60细胞表达Scar1和WASP，用视黄酸或非类视黄醇药物处理诱导其向中性粒细胞分化，导致Scar1表达水平下降，而WASP表达不受影响。用佛波酯处理诱导其向单核细胞/巨噬细胞分化，导致贴壁成熟细胞中这两种蛋白的表达均下降。维生素D(3)处理或细胞松弛素D与PMA联合处理均不影响WASP表达，表明黏附及细胞骨架完整性对调节WASP表达均至关重要。Scar1表达受分化、黏附及细胞骨架完整性的调节。最近发现WASP在足体中与肌动蛋白共定位。相比之下，我们在此表明，在成熟单核细胞/巨噬细胞中，Scar1并不定位于足体。这些观察结果首次表明，Scar1和WASP表达的调节是髓系前体细胞分化程序的一个组成部分，并表明WASP和Scar1在成熟髓细胞中具有不同作用。
