SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C-elegans
SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C-elegans
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DOI：
10.1242/dev.02103
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发表时间：
2005-12-01
期刊：
影响因子：
4.6
通讯作者：
Okada, M
中科院分区：
文献类型：
--
作者：
Itoh, B;Hirose, T;Okada, M
Src家族酪氨酸激酶（SFK）参与动物发育过程中细胞粘附和迁移的调节。我们发现，SRC-1，SFK的直系同源物，在引导秀丽隐杆线虫细胞迁移中起着至关重要的作用。src-1基因的突变导致有缺陷的远端细胞（DTC）指导的性腺形态发生的活动依赖性和DTC细胞自主的方式。在src-1突变体中，DTC不能转向并继续沿腹肌沿着离心迁移。src-1突变的作用被CED/Rac通路中起作用的基因突变抑制，表明DTC中的SRC-1是控制细胞骨架重塑的Rac通路的上游调节因子。在src-1突变体中，uuc-5/netrin受体的表达受到正常调节，并且nc-5的过早表达和unc-5基因的突变都不显著影响DTC迁移缺陷。这些数据表明SRC-1在DTC中的netrin信号传导中起作用。src-1突变体在Q神经母细胞后代AVM和PVM的迁移和生长锥寻路中也表现出细胞自主性缺陷。然而，SRC-1的这些作用似乎不涉及CED/Rac通路。这些发现表明，SRC-1的功能是响应各种细胞外指导线索，通过不同的信号通路在不同的细胞类型中指导细胞迁移。
Src family tyrosine kinase (SFK) has been implicated in the regulation of cell adhesion and migration during animal development. We show that SRC-1, an ortholog of SFK, plays an essential role in directing cell migration in Caenorhabditis elegaus. The mutation in the src-1 gene results in defective distal tip cell (DTC)-directed gonad morphogenesis in an activity-dependent and DTC cell-autonomous manners. In the src-1 mutants, DTCs fail to turn and continue their centrifugal migration along the ventral muscles. The effect of the src-1 mutation is suppressed by mutations in genes that function in the CED/Rac pathway, suggesting that SRC-1 in DTCs is an upstream regulator of a Rac pathway that controls cytoskeletal remodeling. In the src-1 mutant, the expression of uuc-5/netrin receptor is normally regulated, and neither the precocious expression of UNC-5 nor the mutation in the unc-5 gene significantly affects the DTC migration defect. These data suggest that SRC-1 acts in the netrin signaling in DTCs. The src-1 mutant also exhibits cell-autonomous defects in the migration and growth cone path-finding of Q neuroblast descendants AVM and PVM. However, these roles of SRC-1 do not appear to involve the CED/Rac pathway. These findings show that SRC-1 functions in responding to various extracellular guidance cues that direct the cell migration via disparate signaling pathways in different cell types.