Investigating the in vivo role of Carboxyl-terminal Domain of Wntless protein in Zebrafish embryonic development
Date Issued
2015
Date
2015
Author(s)
Lin, Bang-Chi
Abstract
Wnt is a secreted ligand and involved in numerous cell-cell signaling processes, especially in embryo development and tissue homeostasis. Comparing to the understanding of the responding signaling in Wnt-receiving cells, the sorting and secretion of Wnt in Wnt-producing cell is less clear. Wntless (Wls, also known as Gpr177 in mammal) plays a crucial role in carrying Wnts from Golgi to plasma membrane. Although several important functional motifs of Wls have been identified, whether the carboxyl-terminal domain of Wls is functional in zebrafish embryonic development is unknown. I have evaluated the abilities of different truncated Wls proteins in rescuing the inner ear and jaw cartilage defects of wls mutants. I found that neither the carboxyl-terminal 49 amino acids deleted form nor the form containing only the carboxyl-terminal 49 a.a rescue the defects of wls mutants. These data indicate that the carboxyl terminal 49 amino acids are important for Wls function in modulating Wls-mediated development in zebrafish embryo. In addition, utilizing antibody against Wls carboxyl-terminal 49 amino acids, I found the subcellular location of the truncated Wls containing only the carboxyl-terminal 49 a.a or carrying a.a. 221-420 deletion is distinct from endogenous Wls. I suggest these deleted region are both required for Wls subcellular sorting.
Subjects
Wnt signaling pathway
Retromer
Zebrafish
Type
thesis
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