Mammalian CARMIL inhibits actin filament capping by capping protein

Changsong Yang; Martin Pring; Martin A. Wear; Minzhou Huang; John A. Cooper; Tatyana M. Svitkina; Sally H. Zigmond

doi:10.1016/j.devcel.2005.06.008

Mammalian CARMIL inhibits actin filament capping by capping protein

Changsong Yang, Martin Pring, Martin A. Wear, Minzhou Huang, John A. Cooper, Tatyana M. Svitkina, Sally H. Zigmond

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

105 Scopus citations

Abstract

Actin polymerization in cells occurs via filament elongation at the barbed end. Proteins that cap the barbed end terminate this elongation. Heterodimeric capping protein (CP) is an abundant and ubiquitous protein that caps the barbed end. We find that the mouse homolog of the adaptor protein CARMIL (mCARMIL) binds CP with high affinity and decreases its affinity for the barbed end. Addition of mCARMIL to cell extracts increases the rate and extent of Arp2/3 or spectrin-actin seed-induced polymerization. In cells, GFP-mCARMIL concentrates in lamellipodia and increases the fraction of cells with large lamellipodia. Decreasing mCARMIL levels by siRNA transfection lowers the F-actin level and slows cell migration through a mechanism that includes decreased lamellipodia protrusion. This phenotype is reversed by full-length mCARMIL but not mCARMIL lacking the domain that binds CP. Thus, mCARMIL is a key regulator of CP and has profound effects on cell behavior.

Original language	English
Pages (from-to)	209-221
Number of pages	13
Journal	Developmental cell
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.devcel.2005.06.008
State	Published - Aug 2005

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@article{64d4ac8ffb684b16989709e655e63783,

title = "Mammalian CARMIL inhibits actin filament capping by capping protein",

abstract = "Actin polymerization in cells occurs via filament elongation at the barbed end. Proteins that cap the barbed end terminate this elongation. Heterodimeric capping protein (CP) is an abundant and ubiquitous protein that caps the barbed end. We find that the mouse homolog of the adaptor protein CARMIL (mCARMIL) binds CP with high affinity and decreases its affinity for the barbed end. Addition of mCARMIL to cell extracts increases the rate and extent of Arp2/3 or spectrin-actin seed-induced polymerization. In cells, GFP-mCARMIL concentrates in lamellipodia and increases the fraction of cells with large lamellipodia. Decreasing mCARMIL levels by siRNA transfection lowers the F-actin level and slows cell migration through a mechanism that includes decreased lamellipodia protrusion. This phenotype is reversed by full-length mCARMIL but not mCARMIL lacking the domain that binds CP. Thus, mCARMIL is a key regulator of CP and has profound effects on cell behavior.",

author = "Changsong Yang and Martin Pring and Wear, {Martin A.} and Minzhou Huang and Cooper, {John A.} and Svitkina, {Tatyana M.} and Zigmond, {Sally H.}",

note = "Funding Information: The work was supported by NIH grants AI 19883 to S.H.Z., GM070898 to T.M.S., and GM 38542 to J.A.C. We thank Michael Joyce for excellent technical assistance, D. Schafer for anti-CP antibody, M.M. Chou for human Northern blot, S. EauClaire for preliminary experiments of CP/C-1 binding, and J. Hammer for many helpful conversations. ",

year = "2005",

month = aug,

doi = "10.1016/j.devcel.2005.06.008",

language = "English",

volume = "9",

pages = "209--221",

journal = "Developmental cell",

issn = "1534-5807",

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T1 - Mammalian CARMIL inhibits actin filament capping by capping protein

AU - Yang, Changsong

AU - Pring, Martin

AU - Wear, Martin A.

AU - Huang, Minzhou

AU - Cooper, John A.

AU - Svitkina, Tatyana M.

AU - Zigmond, Sally H.

N1 - Funding Information: The work was supported by NIH grants AI 19883 to S.H.Z., GM070898 to T.M.S., and GM 38542 to J.A.C. We thank Michael Joyce for excellent technical assistance, D. Schafer for anti-CP antibody, M.M. Chou for human Northern blot, S. EauClaire for preliminary experiments of CP/C-1 binding, and J. Hammer for many helpful conversations.

PY - 2005/8

Y1 - 2005/8

N2 - Actin polymerization in cells occurs via filament elongation at the barbed end. Proteins that cap the barbed end terminate this elongation. Heterodimeric capping protein (CP) is an abundant and ubiquitous protein that caps the barbed end. We find that the mouse homolog of the adaptor protein CARMIL (mCARMIL) binds CP with high affinity and decreases its affinity for the barbed end. Addition of mCARMIL to cell extracts increases the rate and extent of Arp2/3 or spectrin-actin seed-induced polymerization. In cells, GFP-mCARMIL concentrates in lamellipodia and increases the fraction of cells with large lamellipodia. Decreasing mCARMIL levels by siRNA transfection lowers the F-actin level and slows cell migration through a mechanism that includes decreased lamellipodia protrusion. This phenotype is reversed by full-length mCARMIL but not mCARMIL lacking the domain that binds CP. Thus, mCARMIL is a key regulator of CP and has profound effects on cell behavior.

AB - Actin polymerization in cells occurs via filament elongation at the barbed end. Proteins that cap the barbed end terminate this elongation. Heterodimeric capping protein (CP) is an abundant and ubiquitous protein that caps the barbed end. We find that the mouse homolog of the adaptor protein CARMIL (mCARMIL) binds CP with high affinity and decreases its affinity for the barbed end. Addition of mCARMIL to cell extracts increases the rate and extent of Arp2/3 or spectrin-actin seed-induced polymerization. In cells, GFP-mCARMIL concentrates in lamellipodia and increases the fraction of cells with large lamellipodia. Decreasing mCARMIL levels by siRNA transfection lowers the F-actin level and slows cell migration through a mechanism that includes decreased lamellipodia protrusion. This phenotype is reversed by full-length mCARMIL but not mCARMIL lacking the domain that binds CP. Thus, mCARMIL is a key regulator of CP and has profound effects on cell behavior.

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DO - 10.1016/j.devcel.2005.06.008

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SN - 1534-5807

VL - 9

SP - 209

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JO - Developmental cell

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ER -

Mammalian CARMIL inhibits actin filament capping by capping protein

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