Abstract
Wnt family are conserved secreted proteins required for developmental patterning and tissue homeostasis. Research into the mechanisms that influence intracellular maturation and intercelluar signal transduction of Wnt proteins has proved fruitful. However, the knowledge of how Wnt enters into the endoplasmic reticulum (ER) for processing and secretion is still limited. Here we report that CATP-8/P5A-ATPase directs neuronal migration in C. elegans by controlling EGL-20/Wnt biogenesis. Our genetic and biochemical analyses demonstrate that CATP-8 control the ER targeting of EGL-20/Wnt through the hydrophobic core region in EGL-20 signal sequence. We further show that regulation of Wnt biogenesis by P5A-ATPase is conserved in human cells. These findings reveal physiological roles of P5A-ATPase in neuronal development and identify Wnt proteins as direct substrates of P5A-ATPase to be translocated into the ER.
Competing Interest Statement
The authors have declared no competing interest.
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