Cleavage of the Wnt Receptor Ryk Regulates Neuronal Differentiation during Cortical Neurogenesis

• Published in: Developmental cell Vol. 15; no. 5; pp. 773 - 780
• Main Authors: Lyu, Jungmook, Yamamoto, Vicky, Lu, Wange
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01-11-2008; Cell Press
• Subjects: Active Transport, Cell Nucleus; Amyloid Precursor Protein Secretases - metabolism; Animals; Biological and medical sciences; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Nucleus - metabolism; Cell physiology; Cell receptors; Cell structures and functions; Cercopithecus aethiops; COS Cells; Embryo, Mammalian - metabolism; Fundamental and applied biological sciences. Psychology; Mice; Miscellaneous; Molecular and cellular biology; MOLNEURO; Neurons - cytology; Protein Structure, Tertiary; Receptor Protein-Tyrosine Kinases - chemistry; Receptor Protein-Tyrosine Kinases - metabolism; Signal Transduction; SIGNALING; Stem Cells - cytology; Wnt Proteins - metabolism; Wnt3 Protein; MOLNEURO; SIGNALING; Regulation(control); Neuron; Development; Differentiation; Neurogenesis; Cell signaling; Biological receptor
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2008.10.004

Ryk is a transmembrane receptor tyrosine kinase (RTK). It functions as a receptor of Wnt proteins required for cell-fate determination, axon guidance, and neurite outgrowth in different organisms; however, the molecular mechanism of Ryk signaling is unknown. Here, we show that Ryk is cleaved, permitting the intracellular C-terminal fragment of Ryk to translocate to the nucleus in response to Wnt3 stimulation. We also show that the cleaved intracellular domain of Ryk is required for Wnt3-induced neuronal differentiation in vitro and in vivo. These results demonstrate an unexpected mechanism of signal transduction for Ryk as a Wnt receptor, in which the intracellular domain itself functions as the transducing molecule to bring extracellular signals from the cell surface into the nucleus, to regulate neural progenitor cell differentiation.