Requirement of pointed-end capping by tropomodulin to maintain actin filament length in embryonic chick cardiac myocytes

Nature ◽  
1995 ◽  
Vol 377 (6544) ◽  
pp. 83-86 ◽  
Author(s):  
Carol C. Gregorio ◽  
Annemarie Weber ◽  
Meredith Bondad ◽  
Cynthia R. Pennise ◽  
Velia M. Fowler
Keyword(s):  
Cardiac Myocytes ◽  
Actin Filament ◽  
Embryonic Chick ◽  
Filament Length ◽  
End Capping ◽  
Pointed End

scholarly journals Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility

2003 ◽  
Vol 161 (2) ◽  
pp. 371-380 ◽  
Author(s):  
Robert S. Fischer ◽  
Kimberly L. Fritz-Six ◽  
Velia M. Fowler
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Actin Filament ◽  
Actin Filaments ◽  
Critical Role ◽  
Leading Edge ◽  
Average Cell ◽  
Transient Overexpression ◽  
End Capping ◽  
Pointed End

Actin filament pointed-end dynamics are thought to play a critical role in cell motility, yet regulation of this process remains poorly understood. We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular endothelial cells (HMEC-1). Tmod3 is present in sufficient quantity to cap pointed ends of actin filaments, localizes to actin filament structures in HMEC-1 cells, and appears enriched in leading edge ruffles and lamellipodia. Transient overexpression of GFP–Tmod3 leads to a depolarized cell morphology and decreased cell motility. A fivefold increase in Tmod3 results in an equivalent decrease in free pointed ends in the cells. Unexpectedly, a decrease in the relative amounts of F-actin, free barbed ends, and actin-related protein 2/3 (Arp2/3) complex in lamellipodia are also observed. Conversely, decreased expression of Tmod3 by RNA interference leads to faster average cell migration, along with increases in free pointed and barbed ends in lamellipodial actin filaments. These data collectively demonstrate that capping of actin filament pointed ends by Tmod3 inhibits cell migration and reveal a novel control mechanism for regulation of actin filaments in lamellipodia.

scholarly journals Crystal Structure of the C-Terminal Half of Tropomodulin and Structural Basis of Actin Filament Pointed-End Capping

2002 ◽  
Vol 83 (5) ◽  
pp. 2716-2725 ◽  
Author(s):  
Inna Krieger ◽  
Alla Kostyukova ◽  
Atsuko Yamashita ◽  
Yasushi Nitanai ◽  
Yuichiro Maéda
Keyword(s):  
Crystal Structure ◽  
Actin Filament ◽  
Structural Basis ◽  
End Capping ◽  
Pointed End

scholarly journals Tropomodulins: Pointed-end capping proteins that regulate actin filament architecture in diverse cell types

Cytoskeleton ◽  
2012 ◽  
Vol 69 (6) ◽  
pp. 337-370 ◽  
Author(s):  
Sawako Yamashiro ◽  
David S. Gokhin ◽  
Sumiko Kimura ◽  
Roberta B. Nowak ◽  
Velia M. Fowler
Keyword(s):  
Actin Filament ◽  
Cell Types ◽  
Capping Proteins ◽  
End Capping ◽  
Pointed End

scholarly journals Mechanism of actin filament pointed-end capping by tropomodulin

Science ◽  
2014 ◽  
Vol 345 (6195) ◽  
pp. 463-467 ◽  
Author(s):  
J. N. Rao ◽  
Y. Madasu ◽  
R. Dominguez
Keyword(s):  
Actin Filament ◽  
End Capping ◽  
Pointed End

scholarly journals Tropomodulin Contains Two Actin Filament Pointed End-capping Domains

2003 ◽  
Vol 278 (41) ◽  
pp. 40000-40009 ◽  
Author(s):  
Velia M. Fowler ◽  
Norma J. Greenfield ◽  
Jeannette Moyer
Keyword(s):  
Actin Filament ◽  
End Capping ◽  
Pointed End

scholarly journals Coordinated regulation of platelet actin filament barbed ends by gelsolin and capping protein.

1996 ◽  
Vol 134 (2) ◽  
pp. 389-399 ◽  
Author(s):  
K Barkalow ◽  
W Witke ◽  
D J Kwiatkowski ◽  
J H Hartwig
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filament ◽  
Actin Polymerization ◽  
Residual Activity ◽  
Human Platelets ◽  
Actin Assembly ◽  
Capping Protein ◽  
Capping Proteins ◽  
End Capping ◽  
Human And Mouse

Exposure of cryptic actin filament fast growing ends (barbed ends) initiates actin polymerization in stimulated human and mouse platelets. Gelsolin amplifies platelet actin assembly by severing F-actin and increasing the number of barbed ends. Actin filaments in stimulated platelets from transgenic gelsolin-null mice elongate their actin without severing. F-actin barbed end capping activity persists in human platelet extracts, depleted of gelsolin, and the heterodimeric capping protein (CP) accounts for this residual activity. 35% of the approximately 5 microM CP is associated with the insoluble actin cytoskeleton of the resting platelet. Since resting platelets have an F-actin barbed end concentration of approximately 0.5 microM, sufficient CP is bound to cap these ends. CP is released from OG-permeabilized platelets by treatment with phosphatidylinositol 4,5-bisphosphate or through activation of the thrombin receptor. However, the fraction of CP bound to the actin cytoskeleton of thrombin-stimulated mouse and human platelets increases rapidly to approximately 60% within 30 s. In resting platelets from transgenic mice lacking gelsolin, which have 33% more F-actin than gelsolin-positive cells, there is a corresponding increase in the amount of CP associated with the resting cytoskeleton but no change with stimulation. These findings demonstrate an interaction between the two major F-actin barbed end capping proteins of the platelet: gelsolin-dependent severing produces barbed ends that are capped by CP. Phosphatidylinositol 4,5-bisphosphate release of gelsolin and CP from platelet cytoskeleton provides a mechanism for mediating barbed end exposure. After actin assembly, CP reassociates with the new actin cytoskeleton.

scholarly journals Side-binding proteins modulate actin filament dynamics

2014 ◽  
Author(s):  
Alvaro H. Crevenna ◽  
Marcelino Arciniega ◽  
Aurelie Dupont ◽  
Kaja Kowalska ◽  
Oliver Lange ◽  
...  
Keyword(s):  
Actin Filament ◽  
Brownian Dynamics ◽  
Actin Polymerization ◽  
Actin Dynamics ◽  
Central Feature ◽  
Filament Dynamics ◽  
Filament Structure ◽  
The Rich ◽  
Dynamics Simulations ◽  
Pointed End

Actin filament dynamics govern many key physiological processes from cell motility to tissue morphogenesis. A central feature of actin dynamics is the capacity of the filament to polymerize and depolymerize at its ends in response to cellular conditions. It is currently thought that filament kinetics can be described by a single rate constant for each end. Here, using direct visualization of single actin filament elongation, we show that actin polymerization kinetics at both filament ends are strongly influenced by proteins that bind to the lateral filament surface. We also show that the less dynamic end, called the pointed-end, has a non-elongating state that dominates the observed filament kinetic asymmetry. Estimates of filament flexibility and Brownian dynamics simulations suggest that the observed kinetic diversity arises from structural alteration. Tuning filament kinetics by exploiting the natural malleability of the actin filament structure may be a ubiquitous mechanism to generate the rich variety of observed cellular actin dynamics.

Cellular energy utilization and supply during hypoxia in embryonic cardiac myocytes

1996 ◽  
Vol 270 (1) ◽  
pp. L44-L53 ◽  
Author(s):  
G. R. Budinger ◽  
N. Chandel ◽  
Z. H. Shao ◽  
C. Q. Li ◽  
A. Melmed ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Myocytes ◽  
Energy Demand ◽  
Adenine Nucleotide ◽  
Energy Utilization ◽  
Embryonic Chick ◽  
O2 Uptake ◽  
Progressive Hypoxia ◽  
Cellular Hypoxia

Studies of intact hearts suggest that cardiac myocytes may have the ability to reversibly suppress metabolic activity and energy demand in states of regional hypoperfusion. However, an ability to suppress respiration in response to hypoxia has never been demonstrated in isolated myocytes. To test this, isolated embryonic chick cardiac myocytes were exposed to progressive hypoxia while their rate of O2 uptake and concentrations of lactate, ATP, ADP, AMP, and phosphocreatine were measured. Compared with the value obtained at an oxygen tension (PO2) of 120 Torr, cellular O2 uptake decreased by 28 +/- 14% (SD) at PO2 = 50 Torr and by 64 +/- 25% at PO2 = 20 Torr (P < 0.05). This decrease was similar after 1 min or 2 h of hypoxia, was sustained for 16 h, and was completely reversible within 2 min after reoxygenation. The reduction in O2 uptake was associated with a decrease in the rate of ATP turnover, but no change in adenine nucleotide or phosphocreatine concentrations. In myocytes adherent to glass cover-slips, O2 uptake and contractile motion were decreased after 30-60 min at 50 and 20 Torr, compared with normoxic values. O2 uptake also was significantly decreased at 50 and 20 Torr in myocytes incubated with N,N,N',N'-tetramethyl-p-phenylenediamine, which suggests that the catalytic activity of cytochrome-c oxidase was partially inhibited during hypoxia. In summary, these results demonstrate that embryonic chick cardiac myocytes can suppress their rates of ATP demand, ATP utilization, and O2 uptake during moderate hypoxia through a mechanism that involves a reversible inhibition of cytochrome-c oxidase. This mechanism may represent a protective response to cellular hypoxia.

scholarly journals Vinculin Is a Dually Regulated Actin Filament Barbed End-capping and Side-binding Protein

2010 ◽  
Vol 285 (30) ◽  
pp. 23420-23432 ◽  
Author(s):  
Christophe Le Clainche ◽  
Satya Prakash Dwivedi ◽  
Dominique Didry ◽  
Marie-France Carlier
Keyword(s):  
Actin Filament ◽  
Binding Protein ◽  
End Capping
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