Role of VASP phosphorylation for the regulation of microglia chemotaxis via the regulation of focal adhesion formation/maturation.
Role of VASP phosphorylation for the regulation of microglia chemotaxis via the regulation of focal adhesion formation/maturation.
复制标题
VASP磷酸化在调节小胶质细胞趋化性的作用，通过调节局灶性形成/成熟。
DOI：
10.1016/j.mcn.2009.08.010
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发表时间：
2009-12
影响因子：
3.5
通讯作者：
Chung, C. Y.
中科院分区：
文献类型：
--
作者：
Lee, S.;Chung, C. Y.
Microglia activation and migration are known to play crucial roles for the response to brain injuries. Extracellular ADP was reported to induce microglia chemotaxis and membrane ruffles through P2Y12 receptor. In this study, we examined the role of VASP phosphorylation in ADP-induced microglia chemotaxis and membrane ruffle formation. ADP stimulation transiently increased intracellular cAMP level, VASP phosphorylation at Ser153, membrane ruffle formation, and chemotaxis. PKA inhibitor effectively inhibited VASP phosphorylation and chemotaxis, indicating that P2Y12-mediated activation of PKA and subsequent VASP phosphorylation are involved in the regulation of microglia chemotaxis. Forskolin and Okadaic acid induced sustained VASP phosphorylation at high level, causing a significant reduction of the retraction of membrane ruffles and chemotaxis. In Forskolin- or Okadaic acid-treated cells, phosphorylated VASP remained at the membrane cortex and size and number of mature focal adhesions was not increased, indicating that prolonged phosphorylation of VASP could inhibit transformation of focal complexes into focal adhesions. VASP knock-down cells showed markedly reduced frequency and distance of membrane ruffling upon ADP stimulation, reinforcing the idea that VASP is required for the ruffle formation. Cells expressing GFP-VASPS153A also showed a significant reduction of protrusion distance during ruffle formation, but the frequency and distance of retraction was not affected by FSK at all. This result suggests that dephosphorylation of VASP might be required for the growth of adhesion strength during membrane retraction. Our results suggest that VASP phophorylation by PKA plays an important role in membrane ruffle formation and chemotaxis via the regulation of focal adhesion formation/maturation.
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