Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis.
Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis.
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DOI：
10.1371/journal.pone.0008981
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发表时间：
2010-02-01
期刊：
影响因子：
3.7
通讯作者：
Goodrich LV
中科院分区：
文献类型：
--
作者：
Abraira VE;Satoh T;Fekete DM;Goodrich LV
LRIG基因编码一系列跨膜蛋白，与肿瘤发生、牛皮癣、神经脊发育和复杂的组织形态发生有关。这些不同的表型是否反映了单一的潜在细胞机制尚不清楚。然而，LRIG蛋白含有进化上保守的胞外结构域，既含有富含亮氨酸的重复序列，又含有免疫球蛋白结构域，这表明有能力与共同的伴侣结合。以前的研究表明，Lrig1通过诱导受体内化和降解来结合和抑制ErbB受体酪氨酸激酶家族的成员。此外，Lrig1和Lrig3的其他受体酪氨酸激酶结合伙伴已经被发现，这留下了一个悬而未决的问题，即ErbB信号缺陷是否是所观察到的小鼠表型的原因。在这里，我们报道了Lrig3和Lrig1一样，能够在体外与ErbB受体相互作用。我们研究了这些相互作用在内耳的体内意义，在内耳，Lrig3通过确定Netrin1在耳泡上皮细胞中表达的时间和程度来控制半规管的形成。我们发现ErbB2和ErbB3存在于早期耳廓上皮中，并且Lrig3在这里以细胞自主的方式发挥作用，如果Lrig3调节ErbB2/B3的活性，就可以预测到这一点。然而，抑制鸡耳小泡中ErbB的激活对Netrin基因的表达或通道的形态形成没有明显的影响。我们的结果表明，虽然Lrig1和Lrig3在体外都能与ErbB受体相互作用，但NeuRegin信号的调节不太可能参与依赖Lrig3的内耳形态发生过程。这些结果突出了Lrig1和Lrig3相似的结合特性，并强调了确定这两个家族成员如何与不同的受体结合并调节不同的受体，以影响体内细胞行为的不同方面的必要性。
The Lrig genes encode a family of transmembrane proteins that have been implicated in tumorigenesis, psoriasis, neural crest development, and complex tissue morphogenesis. Whether these diverse phenotypes reflect a single underlying cellular mechanism is not known. However, Lrig proteins contain evolutionarily conserved ectodomains harboring both leucine-rich repeats and immunoglobulin domains, suggesting an ability to bind to common partners. Previous studies revealed that Lrig1 binds to and inhibits members of the ErbB family of receptor tyrosine kinases by inducing receptor internalization and degradation. In addition, other receptor tyrosine kinase binding partners have been identified for both Lrig1 and Lrig3, leaving open the question of whether defective ErbB signaling is responsible for the observed mouse phenotypes. Here, we report that Lrig3, like Lrig1, is able to interact with ErbB receptors in vitro. We examined the in vivo significance of these interactions in the inner ear, where Lrig3 controls semicircular canal formation by determining the timing and extent of Netrin1 expression in the otic vesicle epithelium. We find that ErbB2 and ErbB3 are present in the early otic epithelium, and that Lrig3 acts cell-autonomously here, as would be predicted if Lrig3 regulates ErbB2/B3 activity. However, inhibition of ErbB activation in the chick otic vesicle has no detectable effect on Netrin gene expression or canal morphogenesis. Our results suggest that although both Lrig1 and Lrig3 can interact with ErbB receptors in vitro, modulation of Neuregulin signaling is unlikely to contribute to Lrig3-dependent processes of inner ear morphogenesis. These results highlight the similar binding properties of Lrig1 and Lrig3 and underscore the need to determine how these two family members bind to and regulate different receptors to affect diverse aspects of cell behavior in vivo.
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DOI：
10.1242/dev.029330
发表时间：
2008-12
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Abraira VE;Del Rio T;Tucker AF;Slonimsky J;Keirnes HL;Goodrich LV
通讯作者：
Goodrich LV
BMP4对于检测角头运动的前庭设备的形成至关重要。
影响因子：
4.5
作者：
Chang, Weise;Lin, Zhengshi;Kulessa, Holger;Hebert, Jean;Hogan, Brigid L. M.;Wu, Doris K.
通讯作者：
Wu, Doris K.
影响因子：
11.4
作者：
Gur, G;Rubin, C;Yarden, Y
通讯作者：
Yarden, Y
影响因子：
12.7
作者：
Guo, DS;Nilsson, J;Henriksson, R
通讯作者：
Henriksson, R
影响因子：
5.3
作者：
Ledda, Fernanda;Bieraugel, Oliver;Paratcha, Gustavo
通讯作者：
Paratcha, Gustavo