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Phosphoinositide-binding interface proteins involved in shaping cell membranes.

Takenawa T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: The mechanism by which cell and cell membrane shapes are created has long been a subject of great interest.Among the phosphoinositide-binding proteins, a group of proteins that can change the shape of membranes, in addition to the phosphoinositide-binding ability, has been found.Furthermore, these proteins not only bind to phosphoinositide, but also to the N-WASP/WAVE complex and the actin polymerization machinery, which generates a driving force to shape the membranes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Lipid Biochemistry, Graduate School of Medicine, Kobe University, Hyogo, Japan. takenawa@med.kobe-u.ac.jp

ABSTRACT
The mechanism by which cell and cell membrane shapes are created has long been a subject of great interest. Among the phosphoinositide-binding proteins, a group of proteins that can change the shape of membranes, in addition to the phosphoinositide-binding ability, has been found. These proteins, which contain membrane-deforming domains such as the BAR, EFC/F-BAR, and the IMD/I-BAR domains, led to inward-invaginated tubes or outward protrusions of the membrane, resulting in a variety of membrane shapes. Furthermore, these proteins not only bind to phosphoinositide, but also to the N-WASP/WAVE complex and the actin polymerization machinery, which generates a driving force to shape the membranes.

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Related in: MedlinePlus

Activation mechanism of N-WASP and WAVE. N-WASP has an N-terminal WASP-homology 1 (WH1) domain, where WIP, CR16, or WICH bind. WAVE2 has an N-terminal WAVE-/SCAR-homology domain (WHD/SHD) that mediates protein complex formation with HSPC300, Abi, Nap1, and PIR121/Sra1. The basic region (B) is common to both N-WASP and WAVE2, where phosphoinositides (PIP2 or PIP3) bind for protein localization or activation of the Arp2/3 complex. N-WASP has the Cdc42-Rac-interactive binding region (CRIB) for Cdc42 binding. WAVE2 binds to Rac through PIR121/Sra1 in the WAVE2 complex, and through IRSp53, which binds to the proline-rich (Pro-rich) region of WAVE2. F-BAR containing proteins such as Toca-1 and FBP-7 bind to proline-rich regions of N-WASP, providing the driving force for membrane deformation. On the other hand, IMD/I-BAR of IRSp53 binds to proline-rich regions of WAVE, which generates protrusive force.
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fig04: Activation mechanism of N-WASP and WAVE. N-WASP has an N-terminal WASP-homology 1 (WH1) domain, where WIP, CR16, or WICH bind. WAVE2 has an N-terminal WAVE-/SCAR-homology domain (WHD/SHD) that mediates protein complex formation with HSPC300, Abi, Nap1, and PIR121/Sra1. The basic region (B) is common to both N-WASP and WAVE2, where phosphoinositides (PIP2 or PIP3) bind for protein localization or activation of the Arp2/3 complex. N-WASP has the Cdc42-Rac-interactive binding region (CRIB) for Cdc42 binding. WAVE2 binds to Rac through PIR121/Sra1 in the WAVE2 complex, and through IRSp53, which binds to the proline-rich (Pro-rich) region of WAVE2. F-BAR containing proteins such as Toca-1 and FBP-7 bind to proline-rich regions of N-WASP, providing the driving force for membrane deformation. On the other hand, IMD/I-BAR of IRSp53 binds to proline-rich regions of WAVE, which generates protrusive force.

Mentions: Rapid actin polymerization is induced to form filopodia and lamellipodia when cells move in response to extracellular signals. In general, the barbed ends of actin filaments are capped by large redundant proteins to prevent spontaneous elongation of the filaments in resting cells. Therefore, to trigger rapid actin polymerization for rearrangement of the cortical cytoskeleton and movement in response to extracellular stimuli, cells must expose these barbed ends or form actin nuclei to produce new filaments. We found 2 new proteins—N-WASP19,20) and WAVEs21,55)—that activate actin nucleation proteins, i.e., the Arp2/3 complex,56) and then elongate actin filaments from the sides of the already existing actin filaments (Fig. 4). This results in the mesh-like actin filaments that are typically observed in the leading edges of moving cells.5,6) Thus, this system can bypass the step involving the exposure of barbed ends in order to quickly form mesh-like actin filaments when cells move.


Phosphoinositide-binding interface proteins involved in shaping cell membranes.

Takenawa T - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Activation mechanism of N-WASP and WAVE. N-WASP has an N-terminal WASP-homology 1 (WH1) domain, where WIP, CR16, or WICH bind. WAVE2 has an N-terminal WAVE-/SCAR-homology domain (WHD/SHD) that mediates protein complex formation with HSPC300, Abi, Nap1, and PIR121/Sra1. The basic region (B) is common to both N-WASP and WAVE2, where phosphoinositides (PIP2 or PIP3) bind for protein localization or activation of the Arp2/3 complex. N-WASP has the Cdc42-Rac-interactive binding region (CRIB) for Cdc42 binding. WAVE2 binds to Rac through PIR121/Sra1 in the WAVE2 complex, and through IRSp53, which binds to the proline-rich (Pro-rich) region of WAVE2. F-BAR containing proteins such as Toca-1 and FBP-7 bind to proline-rich regions of N-WASP, providing the driving force for membrane deformation. On the other hand, IMD/I-BAR of IRSp53 binds to proline-rich regions of WAVE, which generates protrusive force.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108299&req=5

fig04: Activation mechanism of N-WASP and WAVE. N-WASP has an N-terminal WASP-homology 1 (WH1) domain, where WIP, CR16, or WICH bind. WAVE2 has an N-terminal WAVE-/SCAR-homology domain (WHD/SHD) that mediates protein complex formation with HSPC300, Abi, Nap1, and PIR121/Sra1. The basic region (B) is common to both N-WASP and WAVE2, where phosphoinositides (PIP2 or PIP3) bind for protein localization or activation of the Arp2/3 complex. N-WASP has the Cdc42-Rac-interactive binding region (CRIB) for Cdc42 binding. WAVE2 binds to Rac through PIR121/Sra1 in the WAVE2 complex, and through IRSp53, which binds to the proline-rich (Pro-rich) region of WAVE2. F-BAR containing proteins such as Toca-1 and FBP-7 bind to proline-rich regions of N-WASP, providing the driving force for membrane deformation. On the other hand, IMD/I-BAR of IRSp53 binds to proline-rich regions of WAVE, which generates protrusive force.
Mentions: Rapid actin polymerization is induced to form filopodia and lamellipodia when cells move in response to extracellular signals. In general, the barbed ends of actin filaments are capped by large redundant proteins to prevent spontaneous elongation of the filaments in resting cells. Therefore, to trigger rapid actin polymerization for rearrangement of the cortical cytoskeleton and movement in response to extracellular stimuli, cells must expose these barbed ends or form actin nuclei to produce new filaments. We found 2 new proteins—N-WASP19,20) and WAVEs21,55)—that activate actin nucleation proteins, i.e., the Arp2/3 complex,56) and then elongate actin filaments from the sides of the already existing actin filaments (Fig. 4). This results in the mesh-like actin filaments that are typically observed in the leading edges of moving cells.5,6) Thus, this system can bypass the step involving the exposure of barbed ends in order to quickly form mesh-like actin filaments when cells move.

Bottom Line: The mechanism by which cell and cell membrane shapes are created has long been a subject of great interest.Among the phosphoinositide-binding proteins, a group of proteins that can change the shape of membranes, in addition to the phosphoinositide-binding ability, has been found.Furthermore, these proteins not only bind to phosphoinositide, but also to the N-WASP/WAVE complex and the actin polymerization machinery, which generates a driving force to shape the membranes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Lipid Biochemistry, Graduate School of Medicine, Kobe University, Hyogo, Japan. takenawa@med.kobe-u.ac.jp

ABSTRACT
The mechanism by which cell and cell membrane shapes are created has long been a subject of great interest. Among the phosphoinositide-binding proteins, a group of proteins that can change the shape of membranes, in addition to the phosphoinositide-binding ability, has been found. These proteins, which contain membrane-deforming domains such as the BAR, EFC/F-BAR, and the IMD/I-BAR domains, led to inward-invaginated tubes or outward protrusions of the membrane, resulting in a variety of membrane shapes. Furthermore, these proteins not only bind to phosphoinositide, but also to the N-WASP/WAVE complex and the actin polymerization machinery, which generates a driving force to shape the membranes.

Show MeSH
Related in: MedlinePlus