Ptprz1b phosphatase binds Prickle2 to promote its membrane localization

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LE Yao NOVOTNÁ Šárka AGOSTINI MAIA Lorena TOLWINSKI Nicholas S. WINKLER Christoph HARNOŠ Jakub

Rok publikování 2026
Druh Recenzovaný odborný článek
Časopis / Zdroj iScience
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://www.sciencedirect.com/science/article/pii/S2589004226020833
Doi https://doi.org/10.1016/j.isci.2026.116707
Klíčová slova Planar cell polarity signaling; Vangl/Prickle; protein tyrosine phosphatase receptor; membrane localization
Přiložené soubory
Popis The Wnt/planar cell polarity (PCP) pathway plays a critical role in the development and homeostasis of multicellular organisms. Molecularly, it is organized into two core protein complexes, Vangl/Prickle and Dishevelled/Frizzled. Here, we identify the receptor-type tyrosine phosphatase Ptprz1b as a regulator of Prickle membrane retention. Ptprz1b binds Prickle2 through multiple regions and depends on Vangl through formation of a membrane-competent Prickle2 pool rather than direct Ptprz1b-Vangl binding. Loss of ptprz1b impairs Prickle2 membrane localization in zebrafish embryos and increases its turnover at the plasma membrane, while membrane Vangl2 levels remain unchanged. A catalytic trapping mutant of Ptprz1b shows increased Prickle2 binding but reduced membrane retention, supporting an activity-dependent stabilization mechanism. Ptprz1b deficiency leads to defects in PCP-dependent morphogenetic processes, including impaired convergent extension in zebrafish and neural tube closure defects in Xenopus. Together, these findings identify Ptprz1b as a regulator of membrane-associated Prickle2 required for PCP-dependent morphogenesis in vivo.
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