TY - JOUR
T1 - Phosphoinositide Signaling Regulates the Exocyst Complex and Polarized Integrin Trafficking in Directionally Migrating Cells
AU - Thapa, Narendra
AU - Sun, Yue
AU - Schramp, Mark
AU - Choi, Suyong
AU - Ling, Kun
AU - Anderson, Richard A.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) grants (CA104708, GM057549, and P30-CA-014520) to R.A.A. and an American Heart Association Postdoctoral Fellowship (10POST4290052) to N.T. We thank Dr. Shu-Chan Hsu at Rutgers University for generously sharing the antibodies to exocyst complex components and Dr. Wei Guo at University of Pennsylvania for providing the plasmids for GFP-Exo70 and GFP-Exo70-1.
PY - 2012/1/17
Y1 - 2012/1/17
N2 - Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP 2-synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγi2 impaired directional migration, formation of cell polarity, and integrin trafficking to the leading edge. Upon initiation of directional migration, PIPKIγi2 via PIP 2 generation controls the integration of the exocyst complex into an integrin-containing trafficking compartment that requires the talin-binding ability of PIPKIγi2, and talin for integrin recruitment to the leading edge. A PIP 2 requirement is further emphasized by inhibition of PIPKIγi2-regulated directional migration by an Exo70 mutant deficient in PIP 2 binding. These results reveal how phosphoinositide generation orchestrates polarized trafficking of integrin in coordination with talin that links integrins to the actin cytoskeleton, processes that are required for directional migration.
AB - Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP 2-synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγi2 impaired directional migration, formation of cell polarity, and integrin trafficking to the leading edge. Upon initiation of directional migration, PIPKIγi2 via PIP 2 generation controls the integration of the exocyst complex into an integrin-containing trafficking compartment that requires the talin-binding ability of PIPKIγi2, and talin for integrin recruitment to the leading edge. A PIP 2 requirement is further emphasized by inhibition of PIPKIγi2-regulated directional migration by an Exo70 mutant deficient in PIP 2 binding. These results reveal how phosphoinositide generation orchestrates polarized trafficking of integrin in coordination with talin that links integrins to the actin cytoskeleton, processes that are required for directional migration.
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U2 - 10.1016/j.devcel.2011.10.030
DO - 10.1016/j.devcel.2011.10.030
M3 - Article
C2 - 22264730
AN - SCOPUS:84862907595
SN - 1534-5807
VL - 22
SP - 116
EP - 130
JO - Developmental Cell
JF - Developmental Cell
IS - 1
ER -