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Cyclical phosphorylation of LRAP35a and CLASP2 by GSK3β and CK1δ regulates EB1-dependent MT dynamics in cell migration

Cell Rep. 2021-09; 
Shumei Chia, Thomas Leung, Ivan Tan
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摘要

Mammalian cell cytoskeletal reorganization for efficient directional movement requires tight coordination of actomyosin and microtubule networks. In this study, we show that LRAP35a potentiates microtubule stabilization by promoting CLASP2/EB1 interaction besides its complex formation with MRCK/MYO18A for retrograde actin flow. The alternate regulation of these two networks by LRAP35a is tightly regulated by a series of phosphorylation events that dictated its specificity. Sequential phosphorylation of LRAP35a by Protein Kinase A (PKA) and Glycogen Synthase Kinase-3β (GSK3β) initiates the association of LRAP35a with CLASP2, while subsequent binding and further phosphorylation by Casein Kinase 1δ (CK1δ) indu... More

关键词

CK1δ, CLASP, EB1, GSK3β, MRCK, PKA, actin-microtubule crosstalk, cell migration, lamellar actomyosin, microtubule stability