Identification of darlin, a Dictyostelium protein with Armadillo-like repeats that binds to small GTPases and is important for the proper aggregation of developing cells.

Identification of darlin, a Dictyostelium protein with Armadillo-like repeats that binds to small GTPases and is important for the proper aggregation of developing cells.
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darlin 的鉴定,一种具有犰狳样重复序列的盘基网柄菌蛋白,可与小 GTP 酶结合,对于发育中细胞的正确聚集非常重要。

DOI:
10.1091/mbc.9.11.3095
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发表时间:
1998
影响因子:
3.3
通讯作者:
DeLozanne,A
DeLozanne,A
中科院分区:
生物学3区
文献类型:
--
作者:
Vithalani,KK;Parent,CA;Thorn,EM;Penn,M;Larochelle,DA;Devreotes,PN;DeLozanne,A

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我们从网柄细胞裂解物中纯化了一种88-kDa的蛋白质,该蛋白质结合小GTP酶的子集,包括racE、racC、cdc 42 Hs和TC 4 ran,但不结合R-ras或rabB。克隆的基因编码这个88 kDa的蛋白质显示,它含有multiplearmadillo样重复最密切相关的哺乳动物GTP交换因子smgGDS。我们将这种蛋白质命名为darlin(Dictyosteliumarmadillo-like protein)。破坏编码darlin的基因表明,这种蛋白质对于胞质分裂、胞饮、吞噬或发育不是必需的。然而,darlin无效细胞在饥饿时聚集的能力受到严重影响。当在液体培养基下饥饿时,突变细胞不能形成聚集中心和聚集流,这可能是因为cAMP中继信号传导的缺陷。这种缺陷并不是因为darlin突变体无法响应G蛋白刺激而激活腺苷酸环化酶。这些结果表明,darlin蛋白参与了一个信号通路,可能在早期发展过程中调节趋化反应。
We purified fromDictyosteliumlysates an 88-kDa protein that bound to a subset of small GTPases, including racE, racC, cdc42Hs, and TC4ran, but did not bind to R-ras or rabB. Cloning of the gene encoding this 88-kDa protein revealed that it contained multiplearmadillo-like repeats most closely related to the mammalian GTP exchange factor smgGDS. We named this protein darlin (Dictyosteliumarmadillo-like protein). Disruption of the gene encoding darlin demonstrated that this protein is not essential for cytokinesis, pinocytosis, phagocytosis, or development. However, the ability of darlin null cells to aggregate in response to starvation is severely affected. When starved under liquid medium, the mutant cells were unable to form aggregation centers and streams, possibly because of a defect in cAMP relay signaling. This defect was not due to an inability of the darlin mutants to activate adenylate cyclase in response to G protein stimulation. These results suggest that the darlin protein is involved in a signaling pathway that may modulate the chemotactic response during early development.