Mammalian diaphanous-related formin 1 regulates GSK3β-dependent microtubule dynamics required for T cell migratory polarization.

Autor: Baoxia Dong, Steven S Zhang, Wen Gao, Haichun Su, Jun Chen, Fuzi Jin, Ajay Bhargava, Xiequn Chen, Lars Jorgensen, Arthur S Alberts, Jinyi Zhang, Katherine A Siminovitch
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: PLoS ONE, Vol 8, Iss 11, p e80500 (2013)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0080500
Popis: The mammalian diaphanous-related formin (mDia1), a Rho-regulated cytoskeletal modulator, has been shown to promote T lymphocyte chemotaxis and interaction with antigen presenting cells, but the mechanisms underpinning mDia1 roles in these processes have not been defined. Here we show that mDia1(-/-) T cells exhibit impaired lymphocyte function-associated antigen 1 (LFA-1)-mediated T cell adhesion, migration and in vivo trafficking. These defects are associated with impaired microtubule (MT) polarization and stabilization, altered MT dynamics and reduced peripheral clustering of the MT plus-end-protein, adenomatous polyposis coli (APC) in migrating T cells following LFA-1-engagement. Loss of mDia1 also leads to impaired inducible inactivation of the glycogen synthase kinase (GSK) 3β as well as hyperphosphorylation and reduced levels of APC in migrating T cells. These findings identify essential roles for the mDia1 formin in modulating GSK3β-dependent MT contributions to induction of T-cell polarity, adhesion and motility.
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