Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Colleen G. Bilancia; Jonathan D. Winkelman; Denis Tsygankov; Stephanie H. Nowotarski; Jennifer A. Sees; Kate Comber; Lwan Evans; Vinal Lakhani; Will Wood; Timothy C. Elston; David R. Kovar; Mark Peifer

doi:10.1016/j.devcel.2014.01.015

Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Colleen G. Bilancia, Jonathan D. Winkelman, Denis Tsygankov, Stephanie H. Nowotarski, Jennifer A. Sees, Kate Comber, Lwan Evans, Vinal Lakhani, Will Wood, Timothy C. Elston, David R. Kovar, Mark Peifer^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.

Original language	English
Pages (from-to)	394-408
Number of pages	15
Journal	Developmental Cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2014.01.015
Publication status	Published - 24 Feb 2014

Keywords / Materials (for Non-textual outputs)

BARBED-END ASSOCIATION
FILAMENT ELONGATION
ENA/VASP PROTEINS
FLUORESCENCE COMPLEMENTATION
FILOPODIUM FORMATION
CONSERVED MECHANISM
BUNDLING ACTIVITY
CAPPING PROTEINS
FISSION YEAST
LIVING CELLS

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10.1016/j.devcel.2014.01.015

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@article{16b4f59939224e85a5f07f83cae36296,

title = "Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo",

abstract = "Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.",

keywords = "BARBED-END ASSOCIATION, FILAMENT ELONGATION, ENA/VASP PROTEINS, FLUORESCENCE COMPLEMENTATION, FILOPODIUM FORMATION, CONSERVED MECHANISM, BUNDLING ACTIVITY, CAPPING PROTEINS, FISSION YEAST, LIVING CELLS",

author = "Bilancia, {Colleen G.} and Winkelman, {Jonathan D.} and Denis Tsygankov and Nowotarski, {Stephanie H.} and Sees, {Jennifer A.} and Kate Comber and Lwan Evans and Vinal Lakhani and Will Wood and Elston, {Timothy C.} and Kovar, {David R.} and Mark Peifer",

year = "2014",

month = feb,

day = "24",

doi = "10.1016/j.devcel.2014.01.015",

language = "English",

volume = "28",

pages = "394--408",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "4",

}

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T1 - Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

AU - Bilancia, Colleen G.

AU - Winkelman, Jonathan D.

AU - Tsygankov, Denis

AU - Nowotarski, Stephanie H.

AU - Sees, Jennifer A.

AU - Comber, Kate

AU - Evans, Lwan

AU - Lakhani, Vinal

AU - Wood, Will

AU - Elston, Timothy C.

AU - Kovar, David R.

AU - Peifer, Mark

PY - 2014/2/24

Y1 - 2014/2/24

N2 - Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.

AB - Actin regulators facilitate cell migration by controlling cell protrusion architecture and dynamics. As the behavior of individual actin regulators becomes clear, we must address why cells require multiple regulators with similar functions and how they cooperate to create diverse protrusions. We characterized Diaphanous (Dia) and Enabled (Ena) as a model, using complementary approaches: cell culture, biophysical analysis, and Drosophila morphogenesis. We found that Dia and Ena have distinct biochemical properties that contribute to the different protrusion morphologies each induces. Dia is a more processive, faster elongator, paralleling the long, stable filopodia it induces in vivo, while Ena promotes filopodia with more dynamic changes in number, length, and lifetime. Acting together, Ena and Dia induce protrusions distinct from those induced by either alone, with Ena reducing Dia-driven protrusion length and number. Consistent with this, EnaEVH1 binds Dia directly and inhibits DiaFH1FH2-mediated nucleation in vitro. Finally, Ena rescues hemocyte migration defects caused by activated Dia.

KW - BARBED-END ASSOCIATION

KW - FILAMENT ELONGATION

KW - ENA/VASP PROTEINS

KW - FLUORESCENCE COMPLEMENTATION

KW - FILOPODIUM FORMATION

KW - CONSERVED MECHANISM

KW - BUNDLING ACTIVITY

KW - CAPPING PROTEINS

KW - FISSION YEAST

KW - LIVING CELLS

U2 - 10.1016/j.devcel.2014.01.015

DO - 10.1016/j.devcel.2014.01.015

M3 - Article

SN - 1534-5807

VL - 28

SP - 394

EP - 408

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -

Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo

Abstract

Keywords / Materials (for Non-textual outputs)

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