IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development.
IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development.
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DOI：
10.1002/cm.21237
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Thisse C
中科院分区：
文献类型：
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作者：
Fang X;Zhang B;Thisse B;Bloom GS;Thisse C
IQGAP 是调节肌动蛋白组装、胞囊功能、细胞运动、形态发生、粘附和分裂的支架蛋白。脊椎动物表达 3 个家族成员：IQGAP1、IQGAP2 和 IQGAP3。已知 IQGAP1 直接与配体激活的生长因子受体（包括 EGFR、VEGFR2 和 FGFR1）的细胞质尾部结合后，通过 N-WASP 和 Arp2/3 复合物刺激分支肌动蛋白丝成核。相比之下，人们对 IQGAP2 或 IQGAP3 的功能知之甚少。通过对斑马鱼 (Danio rerio) 胚胎进行原位杂交，我们发现 IQGAP1 和 IQGAP2 与离散的组织和器官相关，而 IQGAP3 主要在整个胚胎和幼虫发育过程中的增殖细胞中表达。 IQGAP1 和 IQGAP2 的吗啡啉敲除对胚胎形态影响很小，而 IQGAP3 功能的丧失会影响细胞增殖和细胞运动。 IQGAP3 形态表型与 Ras 或成纤维细胞生长因子受体 1 (FGFR1) 显性失活形式的过度表达所导致的表型相似，表明 IQGAP3 在 FGFR1-Ras-ERK 信号传导中发挥作用。为了支持这一假设，FGFR1 或 Ras 的显性失活形式可以通过共注射斑马鱼 IQGAP3 mRNA 来挽救，这强烈表明 IQGAP3 作为 FGFR1-Ras 信号通路的下游调节剂。
IQGAPs are scaffolding proteins that regulate actin assembly, exocyst function, cell motility, morphogenesis, adhesion and division. Vertebrates express 3 family members: IQGAP1, IQGAP2 and IQGAP3. IQGAP1 is known to stimulate nucleation of branched actin filaments through N-WASP and the Arp2/3 complex following direct binding to cytoplasmic tails of ligand-activated growth factor receptors, including EGFR, VEGFR2 and FGFR1. By contrast, little is known about functions of IQGAP2 or IQGAP3. Using in situ hybridization on whole mount zebrafish (Danio rerio) embryos, we show that IQGAP1 and IQGAP2 are associated with discrete tissues and organs, while IQGAP3 is mainly expressed in proliferative cells throughout embryonic and larval development. Morpholino knockdowns of IQGAP1 and IQGAP2 have little effect on embryo morphology while loss of function of IQGAP3 affects both cell proliferation and cell motility. IQGAP3 morphant phenotypes are similar to those resulting from overexpression of dominant negative forms of Ras or of Fibroblast Growth Factor Receptor 1 (FGFR1), suggesting that IQGAP3 plays a role in FGFR1-Ras-ERK signaling. In support of this hypothesis, dominant negative forms of FGFR1 or Ras could be rescued by co-injection of zebrafish IQGAP3 mRNA, strongly suggesting that IQGAP3 acts as a downstream regulator of the FGFR1-Ras signaling pathway.