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Genetic suppression of a phosphomimic myosin II identifies system-level factors that promote myosin II cleavage furrow accumulation.

Ren Y, West-Foyle H, Surcel A, Miller C, Robinson DN - Mol. Biol. Cell (2014)

Bottom Line: How myosin II localizes to the cleavage furrow in Dictyostelium and metazoan cells remains largely unknown despite significant advances in understanding its regulation.Finally, an engineered myosin II with a longer lever arm (2xELC), producing a highly mechanosensitive motor, could also partially suppress the intragenic 3xAsp.Overall, myosin II accumulation is the result of multiple parallel and partially redundant pathways that comprise a cellular contractility control system.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

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Related in: MedlinePlus

Myosin II accumulation and contractility are governed by a mechanosensitive control system. The flow diagram summarizes our view of how myosin II accumulates at the cleavage furrow and generates cortical tension and contractility, which together drive furrow ingression (Zhang and Robinson, 2005; Poirier et al., 2012). Cortical tension contributes in a complex manner, providing resistance early in furrow ingression and then assistance later in furrow ingression. The racE-14-3-3-myosin II pathway contributes to cell mechanics along the global/polar cortex (Zhou et al., 2010). The gray box encapsulates a cooperative module that includes myosin II and cortexillin I (Zhang and Robinson, 2005; Effler et al., 2006; Luo et al., 2012). The IQGAP1 and 2 proteins antagonize each other to modulate the cooperativity module. IQGAP2 further links back to the spindle signaling proteins, including kinesin 6 and INCENP proteins (Kee et al., 2012). Myosin II assembly is also modulated by myosin II heavy chain kinases (MHCKs), which maintain a free pool of myosin monomer (M0) so that myosin II can assemble where and when it is needed (Yumura et al., 2005; Ren et al., 2009). RMD1 also is required for myosin II accumulation at the cleavage furrow cortex. However, mechanical stress bypasses the RMD1 requirement.
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Figure 8: Myosin II accumulation and contractility are governed by a mechanosensitive control system. The flow diagram summarizes our view of how myosin II accumulates at the cleavage furrow and generates cortical tension and contractility, which together drive furrow ingression (Zhang and Robinson, 2005; Poirier et al., 2012). Cortical tension contributes in a complex manner, providing resistance early in furrow ingression and then assistance later in furrow ingression. The racE-14-3-3-myosin II pathway contributes to cell mechanics along the global/polar cortex (Zhou et al., 2010). The gray box encapsulates a cooperative module that includes myosin II and cortexillin I (Zhang and Robinson, 2005; Effler et al., 2006; Luo et al., 2012). The IQGAP1 and 2 proteins antagonize each other to modulate the cooperativity module. IQGAP2 further links back to the spindle signaling proteins, including kinesin 6 and INCENP proteins (Kee et al., 2012). Myosin II assembly is also modulated by myosin II heavy chain kinases (MHCKs), which maintain a free pool of myosin monomer (M0) so that myosin II can assemble where and when it is needed (Yumura et al., 2005; Ren et al., 2009). RMD1 also is required for myosin II accumulation at the cleavage furrow cortex. However, mechanical stress bypasses the RMD1 requirement.

Mentions: Mechanosensing provides an important mechanism for directing the localization of myosin II and is fundamental to a wide range of cellular and tissue functions (Engler et al., 2006; Luo and Robinson, 2011). We have shown that mechanosensitive accumulation plays a central role in tuning the cleavage furrow concentration of myosin II (Kee et al., 2012; Figure 8). This myosin mechanosensitive accumulation is performed by a three-part sensor, including force amplification through the myosin II lever arm, myosin BTF assembly/disassembly dynamics, and actin filament anchoring by cortexillin I (Ren et al., 2009). Multiscale modeling elucidates how myosin II force sensing and cooperative actin binding couple to myosin II BTF assembly (Luo et al., 2012), and this coupling is further demonstrated by the ability of 2xELC-3xAsp to accumulate at the cleavage furrow. This model quantitatively accounts for the amounts and kinetics of myosin II accumulation in response to applied stresses. However, this mechanosensory system is only part of a larger control system that tunes the total level of myosin II accumulation at the cleavage furrow under diverse mechanical constraints (Kee et al., 2012). In this control system (Figure 8), cortexillin I not only anchors the actin filaments, but it also links to signal transduction proteins (Faix et al., 1998; Mondal et al., 2010). These signaling proteins, including IQGAPs and the chromosomal passenger complex proteins, then reinforce signals that emanate from the mitotic spindle to direct myosin II accumulation. Overall this control system demonstrates that to decipher the recruitment pathways, these redundant systems must be taken into account.


Genetic suppression of a phosphomimic myosin II identifies system-level factors that promote myosin II cleavage furrow accumulation.

Ren Y, West-Foyle H, Surcel A, Miller C, Robinson DN - Mol. Biol. Cell (2014)

Myosin II accumulation and contractility are governed by a mechanosensitive control system. The flow diagram summarizes our view of how myosin II accumulates at the cleavage furrow and generates cortical tension and contractility, which together drive furrow ingression (Zhang and Robinson, 2005; Poirier et al., 2012). Cortical tension contributes in a complex manner, providing resistance early in furrow ingression and then assistance later in furrow ingression. The racE-14-3-3-myosin II pathway contributes to cell mechanics along the global/polar cortex (Zhou et al., 2010). The gray box encapsulates a cooperative module that includes myosin II and cortexillin I (Zhang and Robinson, 2005; Effler et al., 2006; Luo et al., 2012). The IQGAP1 and 2 proteins antagonize each other to modulate the cooperativity module. IQGAP2 further links back to the spindle signaling proteins, including kinesin 6 and INCENP proteins (Kee et al., 2012). Myosin II assembly is also modulated by myosin II heavy chain kinases (MHCKs), which maintain a free pool of myosin monomer (M0) so that myosin II can assemble where and when it is needed (Yumura et al., 2005; Ren et al., 2009). RMD1 also is required for myosin II accumulation at the cleavage furrow cortex. However, mechanical stress bypasses the RMD1 requirement.
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Related In: Results  -  Collection

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Figure 8: Myosin II accumulation and contractility are governed by a mechanosensitive control system. The flow diagram summarizes our view of how myosin II accumulates at the cleavage furrow and generates cortical tension and contractility, which together drive furrow ingression (Zhang and Robinson, 2005; Poirier et al., 2012). Cortical tension contributes in a complex manner, providing resistance early in furrow ingression and then assistance later in furrow ingression. The racE-14-3-3-myosin II pathway contributes to cell mechanics along the global/polar cortex (Zhou et al., 2010). The gray box encapsulates a cooperative module that includes myosin II and cortexillin I (Zhang and Robinson, 2005; Effler et al., 2006; Luo et al., 2012). The IQGAP1 and 2 proteins antagonize each other to modulate the cooperativity module. IQGAP2 further links back to the spindle signaling proteins, including kinesin 6 and INCENP proteins (Kee et al., 2012). Myosin II assembly is also modulated by myosin II heavy chain kinases (MHCKs), which maintain a free pool of myosin monomer (M0) so that myosin II can assemble where and when it is needed (Yumura et al., 2005; Ren et al., 2009). RMD1 also is required for myosin II accumulation at the cleavage furrow cortex. However, mechanical stress bypasses the RMD1 requirement.
Mentions: Mechanosensing provides an important mechanism for directing the localization of myosin II and is fundamental to a wide range of cellular and tissue functions (Engler et al., 2006; Luo and Robinson, 2011). We have shown that mechanosensitive accumulation plays a central role in tuning the cleavage furrow concentration of myosin II (Kee et al., 2012; Figure 8). This myosin mechanosensitive accumulation is performed by a three-part sensor, including force amplification through the myosin II lever arm, myosin BTF assembly/disassembly dynamics, and actin filament anchoring by cortexillin I (Ren et al., 2009). Multiscale modeling elucidates how myosin II force sensing and cooperative actin binding couple to myosin II BTF assembly (Luo et al., 2012), and this coupling is further demonstrated by the ability of 2xELC-3xAsp to accumulate at the cleavage furrow. This model quantitatively accounts for the amounts and kinetics of myosin II accumulation in response to applied stresses. However, this mechanosensory system is only part of a larger control system that tunes the total level of myosin II accumulation at the cleavage furrow under diverse mechanical constraints (Kee et al., 2012). In this control system (Figure 8), cortexillin I not only anchors the actin filaments, but it also links to signal transduction proteins (Faix et al., 1998; Mondal et al., 2010). These signaling proteins, including IQGAPs and the chromosomal passenger complex proteins, then reinforce signals that emanate from the mitotic spindle to direct myosin II accumulation. Overall this control system demonstrates that to decipher the recruitment pathways, these redundant systems must be taken into account.

Bottom Line: How myosin II localizes to the cleavage furrow in Dictyostelium and metazoan cells remains largely unknown despite significant advances in understanding its regulation.Finally, an engineered myosin II with a longer lever arm (2xELC), producing a highly mechanosensitive motor, could also partially suppress the intragenic 3xAsp.Overall, myosin II accumulation is the result of multiple parallel and partially redundant pathways that comprise a cellular contractility control system.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Show MeSH
Related in: MedlinePlus