Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction.
Calreticulin is a secreted BMP antagonist, expressed in Hensen's node during neural induction.
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DOI：
10.1016/j.ydbio.2016.12.001
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发表时间：
2017-01-15
影响因子：
2.7
通讯作者：
Stern CD
中科院分区：
文献类型：
--
作者：
De Almeida I;Oliveira NMM;Randall RA;Hill CS;McCoy JM;Stern CD
亨森结是鸟类和哺乳动物早期胚胎的“组织者”。它具有许多功能，包括神经诱导和外胚层和中胚层的图案化。一些负责这些活动的信号是已知的，但这些并不能解释组织者活动的全部复杂性。在这里，我们进行功能筛选，以发现新的分泌因子表达的节点在这个时候的发展。在酵母中使用信号序列陷阱，我们确定了几个候选人。在这里，我们专注于钙网蛋白。我们发现钙网蛋白除了在细胞内钙调节和蛋白质折叠中具有已知的功能外，还可以分泌，它可以与BMP 4结合，并在体内和体外作为BMP拮抗剂。钙网蛋白不足以解释所有的组织者功能，但可能有助于其活动的复杂性。功能筛选揭示了鸡亨森氏结表达的新分泌因子。酵母信号序列陷阱鉴定了包括钙网蛋白和钙连接蛋白在内的候选因子。我们发现钙网蛋白被分泌并与BMP 4结合。钙网蛋白在体内和体外作为BMP拮抗剂。钙网蛋白不能解释所有的组织者功能，但可能有助于其复杂性。
Hensen's node is the “organizer” of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity. A functional screen uncovers new secreted factors expressed by chick Hensen's node A yeast Signal Sequence Trap identifies candidates including Calreticulin and Calnexin. We show thatCalreticulin is secretedand binds to BMP4. Calreticulin acts as a BMP antagonist in vivo and in vitro. Calreticulin does not account for all organizer functions but may contribute to its complexity.