Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis.

Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis.
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DOI:
10.1083/jcb.146.6.1303
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发表时间:
1999-09-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Bejsovec A
Bejsovec A
中科院分区:
其他
文献类型:
--
作者:
McCartney BM;Dierick HA;Kirkpatrick C;Moline MM;Baas A;Peifer M;Bejsovec A

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肿瘤抑制性腺瘤性结肠息肉病 (APC) 通过帮助靶向 Wnt 效应子 β-连环蛋白或其果蝇同源物犰狳 (Arm) 进行破坏,从而负向调节 Wingless (Wg)/Wnt 信号转导。在培养的哺乳动物细胞中,APC 定位于微管末端附近的细胞皮层。果蝇 APC (dAPC) 负向调节 Arm 信号传导,但仅限于有限的组织。我们描述了第二种果蝇 APC,dAPC2,它结合 Arm 并在广泛的组织中表达。 dAPC2 的亚细胞定位揭示了在许多但并非所有细胞环境中与肌动蛋白的共定位,并且还表明可能与星形微管相互作用。例如,dAPC2 在神经母细胞中具有惊人的不对称分布,并且 dAPC2 与发育中的幼虫小齿基部的组装肌动蛋白丝共定位。我们发现了 dAPC2 突变,表明 dAPC2 是胚胎表皮中 Wg 信号传导的负调节因子。该等位基因在遗传上作用于 wg 下游、arm、dTCF 上游,并且令人惊讶的是,它是蓬乱的。我们讨论了我们的结果对 Wg 信号传导的影响,并提出了 dAPC2 作为 Wg 对细胞骨架影响的中介者的作用。我们还推测 APC 在细胞骨架动力学中可能发挥的更普遍的作用。
The tumor suppressor adenomatous polyposis coli (APC) negatively regulates Wingless (Wg)/Wnt signal transduction by helping target the Wnt effector β-catenin or its Drosophila homologue Armadillo (Arm) for destruction. In cultured mammalian cells, APC localizes to the cell cortex near the ends of microtubules. Drosophila APC (dAPC) negatively regulates Arm signaling, but only in a limited set of tissues. We describe a second fly APC, dAPC2, which binds Arm and is expressed in a broad spectrum of tissues. dAPC2's subcellular localization revealed colocalization with actin in many but not all cellular contexts, and also suggested a possible interaction with astral microtubules. For example, dAPC2 has a striking asymmetric distribution in neuroblasts, and dAPC2 colocalizes with assembling actin filaments at the base of developing larval denticles. We identified a dAPC2 mutation, revealing that dAPC2 is a negative regulator of Wg signaling in the embryonic epidermis. This allele acts genetically downstream of wg, and upstream of arm, dTCF, and, surprisingly, dishevelled. We discuss the implications of our results for Wg signaling, and suggest a role for dAPC2 as a mediator of Wg effects on the cytoskeleton. We also speculate on more general roles that APCs may play in cytoskeletal dynamics.
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