Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/37558
Title: THE ROLE OF WNTLESS / WLS IN THE REGULATION OF WNT SECRETION
Authors: YU JIA
Keywords: Wnt, Wntless, secretion, palmitoylation, trafficking, localization,
Issue Date: 24-Aug-2012
Source: YU JIA (2012-08-24). THE ROLE OF WNTLESS / WLS IN THE REGULATION OF WNT SECRETION. ScholarBank@NUS Repository.
Abstract: The Wnt pathway plays important roles in development and tumorigenesis. We found that the secretion of all human Wnts requires palmitoleate modification at a conserved serine residue, which facilitates Wnts binding to the carrier protein WLS. Based on computational modeling, we proposed that WLS may bind Wnts via a lipid¿binding lipocalin domain. Vacuolar acidification is required to release Wnts from WLS during secretion, possibly to facilitate transfer of Wnts to a soluble carrier protein. It was not previously known how Wnts travel from ER to Golgi during secretion. Using density gradient ultracentrifugation and novel WLS antibodies, I found that endogenous WLS shuttles Wnts from ER to plasma membrane and then WLS recycles back to ER. Mutational analysis confirmed that the carboxyl-terminal sequences of WLS are critical for both ER localization and its biological function. Detailed analysis of WLS Golgi-to-ER traffic revealed new proteins involved in the Wnt secretion pathway.
URI: http://scholarbank.nus.edu.sg/handle/10635/37558
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