Lamellipodial versus filopodial mode of the actin nanomachinery: pivotal role of the filament barbed end.
Understanding how a particular cell type expresses the lamellipodial or filopodial form of the actin machinery is essential to understanding a cell's functional interactions. To determine how a cell "chooses" among these alternative modes of "molecular hardware," we tested the role of key proteins that affect actin filament barbed ends. Depletion of capping protein (CP) by short hairpin RNA (shRNA) caused loss of lamellipodia and explosive formation of filopodia. The knockdown phenotype was rescued by a CP mutant refractory to shRNA, but not by another barbed-end capper, gelsolin, demonstrating that the phenotype was specific for CP. In Ena/VASP deficient cells, CP depletion resulted in ruffling instead of filopodia. We propose a model for selection of lamellipodial versus filopodial organization in which CP is a negative regulator of filopodia formation and Ena/VASP has recruiting/activating functions downstream of actin filament elongation in addition to its previously suggested anticapping and antibranching activities.
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Marisan R
MR
Mejillano
Shin-ichiro
S
Kojima
Derek Anthony
DA
Applewhite
Frank B
FB
Gertler
Tatyana M
TM
Svitkina
Gary G
GG
Borisy
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003598:Cytoskeletal Proteins; D051345:Destrin; D007700:Kinetics; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D010750:Phosphoproteins / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism* / Q000648:ultrastructure; D000098662:Vasodilator-Stimulated Phosphoprotein
D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051345:Destrin; C102176:Enah protein, mouse; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein