Interaction with Notch determines endocytosis of specific Delta ligands in zebrafish neural tissue
Interaction with Notch determines endocytosis of specific Delta ligands in zebrafish neural tissue
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DOI：
10.1242/dev.027938
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发表时间：
2009-01-15
期刊：
影响因子：
4.6
通讯作者：
Chitnis, Ajay B.
中科院分区：
文献类型：
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作者：
Matsuda, Miho;Chitnis, Ajay B.
思维炸弹1（Mib 1）介导的Notch配体DeltaD的内吞作用对于邻近细胞中Notch的激活是必不可少的。虽然大多数DeltaD定位在斑马鱼神经组织的细胞质点，它是在质膜上的mib 1突变体，因为Mib 1介导的内吞作用决定了正常的亚细胞定位的DeltaD。Notch的敲低增加细胞表面DeltaA和DeltaD，但不增加DeltaC，表明Notch与Mib 1一样调节特异性配体的内吞作用。移植实验表明，在同一细胞（顺式）和相邻细胞（反式）中与Notch的相互作用调节DeltaD内吞作用。尽管反式相互作用后的DeltaD内吞作用激活相邻细胞中的Notch，但顺式相互作用后的DeltaD和Notch的内吞作用可能通过使两者在细胞表面不可用来抑制Notch信号传导。移植实验揭示了一个异质群体的祖细胞：在一些，顺式相互作用是更重要的;在其他人，反式相互作用是更重要的;和在其他人，顺式和反式相互作用可能有助于DeltaD内吞。我们认为，这种异质性代表的过程中，有效的侧向抑制导致多样化的祖细胞成细胞，成为专门提供或接收三角洲信号，反式和顺式相互作用与Notch发挥不同的作用在DeltaD内吞。
Mind bomb1 (Mib1)-mediated endocytosis of the Notch ligand DeltaD is essential for activation of Notch in a neighboring cell. Although most DeltaD is localized in cytoplasmic puncta in zebrafish neural tissue, it is on the plasma membrane in mib1 mutants because Mib1-mediated endocytosis determines the normal subcellular localization of DeltaD. Knockdown of Notch increases cell surface DeltaA and DeltaD, but not DeltaC, suggesting that, like Mib1, Notch regulates endocytosis of specific ligands. Transplant experiments show that the interaction with Notch, both in the same cell (in cis) and in neighboring cells (in trans), regulates DeltaD endocytosis. Whereas DeltaD endocytosis following interaction in trans activates Notch in a neighboring cell, endocytosis of DeltaD and Notch following an interaction in cis is likely to inhibit Notch signaling by making both unavailable at the cell surface. The transplantation experiments reveal a heterogeneous population of progenitors: in some, cis interactions are more important; in others, trans interactions are more important; and in others, both cis and trans interactions are likely to contribute to DeltaD endocytosis. We suggest that this heterogeneity represents the process by which effective lateral inhibition leads to diversification of progenitors into cells that become specialized to deliver or receive Delta signals, where trans and cis interactions with Notch play differential roles in DeltaD endocytosis.