Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics

TY - JOUR

T1 - Lamellipodin, an Ena/VASP ligand, is implicated in the regulation of lamellipodial dynamics

AU - Krause, M

AU - Leslie, J D

AU - Stewart, M

AU - Lafuente, E M

AU - Valderrama, F

AU - Jagannathan, R

AU - Strasser, G A

AU - Rubinson, D A

AU - Liu, H

AU - Way, M

AU - Yaffe, M B

AU - Boussiotis, V A

AU - Gertier, F B

PY - 2004/10

Y1 - 2004/10

N2 - Lamellipodial protrusion is regulated by Ena/VASP proteins. We identified Lamellipodin (Lpd) as an Ena/VASP binding protein. Both proteins colocalize at the tips of lamellipodia and filopodia. Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility. Lpd contains a PH domain that binds specifically to PI(3,4)P-2, an asymmetrically localized signal in chemotactic cells. Lpd's PH domain can localize to ruffles in PDGF-treated fibroblasts. Lpd overexpression increases lamellipodial protrusion velocity, an effect observed when Ena/VASP proteins are overexpressed or artificially targeted to the plasma membrane. Conversely, knockdown of Lpd expression impairs lamellipodia formation, reduces velocity of residual lamellipodial protrusion, and decreases F-actin content. These phenotypes are more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors of the actin cytoskeleton in addition to Ena/VASP.

AB - Lamellipodial protrusion is regulated by Ena/VASP proteins. We identified Lamellipodin (Lpd) as an Ena/VASP binding protein. Both proteins colocalize at the tips of lamellipodia and filopodia. Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility. Lpd contains a PH domain that binds specifically to PI(3,4)P-2, an asymmetrically localized signal in chemotactic cells. Lpd's PH domain can localize to ruffles in PDGF-treated fibroblasts. Lpd overexpression increases lamellipodial protrusion velocity, an effect observed when Ena/VASP proteins are overexpressed or artificially targeted to the plasma membrane. Conversely, knockdown of Lpd expression impairs lamellipodia formation, reduces velocity of residual lamellipodial protrusion, and decreases F-actin content. These phenotypes are more severe than loss of Ena/VASP, suggesting that Lpd regulates other effectors of the actin cytoskeleton in addition to Ena/VASP.

U2 - 10.1016/j.devcel.2004.07.024

DO - 10.1016/j.devcel.2004.07.024

M3 - Article

SN - 1878-1551

VL - 7

SP - 571

EP - 583

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -