Abstract
Phosphatidylinositol-4,5-bisphosphate (PI4,5P2) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4- phosphate 5-kinases (PIPKIs), which synthesize PI4,5P2, have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration.
| Original language | English |
|---|---|
| Pages (from-to) | 247-262 |
| Number of pages | 16 |
| Journal | Journal of Cell Biology |
| Volume | 190 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jul 26 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
Cite this
Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation. / Chao, Wei Ting; Daquinag, Alexes C.; Ashcroft, Felicity; Kunz, Jeannette.
In: Journal of Cell Biology, Vol. 190, No. 2, 26.07.2010, p. 247-262.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation
AU - Chao, Wei Ting
AU - Daquinag, Alexes C.
AU - Ashcroft, Felicity
AU - Kunz, Jeannette
PY - 2010/7/26
Y1 - 2010/7/26
N2 - Phosphatidylinositol-4,5-bisphosphate (PI4,5P2) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4- phosphate 5-kinases (PIPKIs), which synthesize PI4,5P2, have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration.
AB - Phosphatidylinositol-4,5-bisphosphate (PI4,5P2) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4- phosphate 5-kinases (PIPKIs), which synthesize PI4,5P2, have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration.
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U2 - 10.1083/jcb.200911110
DO - 10.1083/jcb.200911110
M3 - Article
VL - 190
SP - 247
EP - 262
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 2
ER -