Caspase‐mediated cleavage and activation of LIM‐kinase 1 and its role in apoptotic membrane blebbing

Tomiyoshi, Go; Horita, Yuji; Nishita, Michiru; Ohashi, Kazumasa; Mizuno, Kensaku

doi:10.1111/j.1356-9597.2004.00745.x

Cited by 57 publications

(49 citation statements)

References 39 publications

(59 reference statements)

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“…5B). These membrane blebs are F-actin-rich structures and are also induced by overexpression of active LIMK1 or LIMK2 (43,44), suggesting that the proper level of cofilin/ADF activities is required for retention of the normal round morphology of MM1 cells. Given the important role of cofilin/ADF in actin cytoskeletal dynamics, the extent of the inhibitory effect of cofilin/ADF knockdown on tumor cell invasion may look too small.…”

Section: Discussionmentioning

confidence: 99%

Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase

Horita

Ohashi

Mukai

et al. 2008

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase

Horita

Ohashi

Mukai

et al. 2008

Journal of Biological Chemistry

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“…Plasmids coding for C-terminally YFP-or Discosoma red fluorescent protein (DsRed)-tagged cofilin and its S3A and S3E mutants, cyan fluorescent protein (CFP)-tagged histone H2B (CFP-H2B), and YFP-actin were constructed as described previously (16,24,25). A LIMK1 siRNA plasmid (pSUPER-LIMK1) that targets the human LIMK1 mRNA sequence (nucleotide positions from the start ATG codon, 1416 -1434; GAATGTGGTGGTGGCTGAC) was constructed as described (34). As a control, a mutated LIMK1 siRNA plasmid was constructed by substituting two bases in the target sequence (GAATGTTGTGGTGGCTGCC).…”

Section: Methodsmentioning

confidence: 99%

LIM Kinase-mediated Cofilin Phosphorylation during Mitosis Is Required for Precise Spindle Positioning

Kaji

Muramoto

Mizuno

2008

Journal of Biological Chemistry

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The interaction of astral microtubules with cortical actin networks is essential for the correct orientation of the mitotic spindle; however, little is known about how the cortical actin organization is regulated during mitosis. LIM kinase-1 (LIMK1) regulates actin dynamics by phosphorylating and inactivating cofilin, an actin-depolymerizing protein. LIMK1 activity increases during mitosis. Here we show that mitotic LIMK1 activation is critical for accurate spindle orientation in mammalian cells. Knockdown of LIMK1 suppressed a mitosis-specific increase in cofilin phosphorylation and caused unusual cofilin localization in the cell cortex in metaphase, instability of cortical actin organization and astral microtubules, irregular rotation and misorientation of the spindle, and a delay in anaphase onset. Similar results were obtained by treating the cells with a LIMK1 inhibitor peptide or latrunculin A or by overexpressing a non-phosphorylatable cofilin(S3A) mutant. Furthermore, localization of LGN (a protein containing the repetitive Leu-Gly-Asn tripeptide motifs), an important regulator of spindle orientation, in the crescent-shaped cortical regions was perturbed in LIMK1 knockdown cells. Our results suggest that LIMK1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis.The accurate establishment of the positioning and orientation of the mitotic spindle is essential for cells to determine the axis and plane of cell division and, consequently, to specify the sizes, positions, and fates of daughter cells after mitosis. Proper spindle positioning and orientation are fundamental for both asymmetric and symmetric cell division. Asymmetric cell division produces two unequal daughter cells and is crucial for a number of biological processes including embryogenesis, neurogenesis, tissue remodeling, and stem cell differentiation (1-3). On the other hand, most cells undergo symmetric cell division that is important to give rise to two equal daughter cells. Positioning of the mitotic spindle is regulated by the interaction of astral microtubules that emanate from two spindle poles with specific regions of the cell cortex. A number of proteins have been proposed to mediate this interaction, including microtubule plus-end-associated proteins (such as EB1 and APC), the dynein-dynactin motor protein complex, and other bridging proteins that bind to the actin cytoskeleton or other components in the cell cortex (4 -7). During asymmetric cell division, the spindle orientation is controlled by a set of conserved "spindle-positioning proteins," such as Inscuteable, Partner of Inscuteable (Pins), 2 a G protein ␣ subunit, and the Par3-Par6-aPKC complex, which asymmetrically localize in the cell cortex (1-3). Recent studies have shown that during symmetric cell division of cultured mammalian cells, integrin-mediated cell adhesion guides the proper spindle orientation parallel to the substrate plane through the regulation of the cortical actin cytoskeleton (...

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“…Although mechanoporation induced by the mechanical insult may be one initiating factor for membrane blebbing (by directly decreasing membrane tension through the formation of holes=tears), subsequent events such as oxidative stress, increased intracellular pressure, cytoskeletal alterations, and sodium influx may also cause post-SCI blebbing as observed in other cell types (Cunningham, 1995;Marin-Castano et al, 2005;Rentsch and Keller, 2000;Shi et al, 2005). Plasma membrane blebbing has been associated with apoptosis and necrosis (Barros et al, 2003;Laster and Mackenzie, 1996;Mills et al, 1998;Tomiyoshi et al, 2004), but bleb formation does not necessarily lead to cell death (Hiruma et al, 2007;Marin-Castano et al, 2005;Shi et al, 2005). Future work should be aimed at a better understanding of the causes and effects of membrane blebbing and its relationship to alterations in plasma membrane permeability.…”

Section: Figmentioning

confidence: 98%

Spinal Cord Contusion Causes Acute Plasma Membrane Damage

Simon

Sharif

Tan

et al. 2009

Journal of Neurotrauma

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Spinal cord injury (SCI) launches a complex cascade of events that leads to progressive damage and loss of function. Compromise of plasma membrane integrity due to the mechanical impact is an acute event that may contribute to cellular dysfunction. Therefore, the objective of this study was to better understand the extent of acute plasma membrane damage associated with SCI as a function of injury severity and membrane defect size. Fluorescent cell-impermeant dyes were injected into the cerebrospinal fluid of adult male rats prior to contusion injury, and the anatomical location of cell bodies and axons taking up the dye within 10 min following SCI was quantified. Lucifer yellow uptake was assessed as a function of impact force (experimental groups: sham, 100 kdyn, 150 kdyn, and 200 kdyn force). In a separate group of animals, FITC-conjugated dextran molecules of various sizes (3 kDa and 10 kDa with a 1.6-nm and 2.7-nm radius, respectively) were used to approximate the size of membrane defects following moderate injury (150 kdyn force). Quantification revealed that cellular uptake of lucifer yellow was positively correlated with the force of the mechanical impact, indicating that the severity of injury is related to the degree of acute membrane failure. In addition, after moderate injury, cell bodies and axons (located up to 2 mm and 3 mm from the epicenter, respectively) took up significantly more of the 3-kDa and 10-kDa dextran permeability marker compared to sham controls. Permeable neuronal cell bodies exhibited a morphological appearance characterized by pericellular blebbing, suggesting that plasma membrane compromise is associated with pathophysiological cellular alterations. Collectively, these results enhance our understanding of acute SCI and provide targets for developing novel treatment strategies.

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Caspase‐mediated cleavage and activation of LIM‐kinase 1 and its role in apoptotic membrane blebbing

Cited by 57 publications

References 39 publications

Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase

Suppression of the Invasive Capacity of Rat Ascites Hepatoma Cells by Knockdown of Slingshot or LIM Kinase

LIM Kinase-mediated Cofilin Phosphorylation during Mitosis Is Required for Precise Spindle Positioning

Spinal Cord Contusion Causes Acute Plasma Membrane Damage

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