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: |
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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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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