scholarly journals Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b

2011 ◽  
Vol 208 (9) ◽  
pp. 1777-1787 ◽  
Author(s):  
Niko Föger ◽  
André Jenckel ◽  
Zane Orinska ◽  
Kyeong-Hee Lee ◽  
Andrew C. Chan ◽  
...  
Keyword(s):  
Mast Cell ◽  
Actin Cytoskeleton ◽  
Critical Role ◽  
Cytokine Secretion ◽  
Regulatory Proteins ◽  
Actin Binding ◽  
Filamentous Actin ◽  
Regulatory Pathways ◽  
Proinflammatory Mediators ◽  
Actin Regulatory Proteins

Mast cell (MC) activation via aggregation of the high affinity IgE receptor (FcεRI) causes degranulation and release of proinflammatory mediators in a process that involves the reorganization of the actin cytoskeleton. However, the regulatory pathways and the molecular links between cytoskeletal changes and MC function are incompletely understood. In this study, we provide genetic evidence for a critical role of the actin-regulatory proteins Coronin1a (Coro1a) and Coro1b on exocytic pathways in MCs: Coro1a−/− bone marrow–derived MCs exhibit increased FcεRI-mediated degranulation of secretory lysosomes but significantly reduced secretion of cytokines. Hyperdegranulation of Coro1a−/− MCs is further augmented by the additional loss of Coro1b. In vivo, Coro1a−/−Coro1b−/− mice displayed enhanced passive cutaneous anaphylaxis. Functional reconstitution assays revealed that the inhibitory effect of Coro1a on MC degranulation strictly correlates with cortical localization of Coro1a, requires its filamentous actin–binding activity, and is regulated by phosphorylation of Ser2 of Coro1a. Thus, coronin proteins, and in turn the actin cytoskeleton, exhibit a functional dichotomy as differential regulators of degranulation versus cytokine secretion in MC biology.

scholarly journals Synthetic lethality screen identifies a novel yeast myosin I gene (MYO5): myosin I proteins are required for polarization of the actin cytoskeleton.

1996 ◽  
Vol 133 (6) ◽  
pp. 1277-1291 ◽  
Author(s):  
H V Goodson ◽  
B L Anderson ◽  
H M Warrick ◽  
L A Pon ◽  
J A Spudich
Keyword(s):  
Actin Cytoskeleton ◽  
Synthetic Lethality ◽  
Critical Role ◽  
Neck Region ◽  
Actin Binding ◽  
Cell Physiology ◽  
Deletion Mutants ◽  
Tail Domain ◽  
Amino Terminal ◽  
Myosin I

The organization of the actin cytoskeleton plays a critical role in cell physiology in motile and nonmotile organisms. Nonetheless, the function of the actin based motor molecules, members of the myosin superfamily, is not well understood. Deletion of MYO3, a yeast gene encoding a "classic" myosin I, has no detectable phenotype. We used a synthetic lethality screen to uncover genes whose functions might overlap with those of MYO3 and identified a second yeast myosin 1 gene, MYO5. MYO5 shows 86 and 62% identity to MYO3 across the motor and non-motor regions. Both genes contain an amino terminal motor domain, a neck region containing two IQ motifs, and a tail domain consisting of a positively charged region, a proline-rich region containing sequences implicated in ATP-insensitive actin binding, and an SH3 domain. Although myo5 deletion mutants have no detectable phenotype, yeast strains deleted for both MYO3 and MYO5 have severe defects in growth and actin cytoskeletal organization. Double deletion mutants also display phenotypes associated with actin disorganization including accumulation of intracellular membranes and vesicles, cell rounding, random bud site selection, sensitivity to high osmotic strength, and low pH as well as defects in chitin and cell wall deposition, invertase secretion, and fluid phase endocytosis. Indirect immunofluorescence studies using epitope-tagged Myo5p indicate that Myo5p is localized at actin patches. These results indicate that MYO3 and MYO5 encode classical myosin I proteins with overlapping functions and suggest a role for Myo3p and Myo5p in organization of the actin cytoskeleton of Saccharomyces cerevisiae.

scholarly journals Coxiella burnetii Induces Reorganization of the Actin Cytoskeleton in Human Monocytes

1998 ◽  
Vol 66 (11) ◽  
pp. 5527-5533 ◽  
Author(s):  
Sonia Meconi ◽  
Véronique Jacomo ◽  
Patrice Boquet ◽  
Didier Raoult ◽  
Jean-Louis Mege ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Coxiella Burnetii ◽  
Actin Polymerization ◽  
Q Fever ◽  
Morphological Changes ◽  
Critical Role ◽  
Filamentous Actin ◽  
Cytoskeleton Reorganization ◽  
Membrane Protrusions ◽  
Actin Protrusions

ABSTRACT Coxiella burnetii, an obligate intracellular bacterium which survives in myeloid cells, causes Q fever in humans. We previously demonstrated that virulent C. burnetiiorganisms are poorly internalized by monocytes compared to avirulent variants. We hypothesized that a differential mobilization of the actin cytoskeleton may account for this distinct phagocytic behavior. Scanning electron microscopy demonstrated that virulent C. burnetii stimulated profound and polymorphic changes in the morphology of THP-1 monocytes, consisting of membrane protrusions and polarized projections. These changes were transient, requiring 5 min to reach their maximum extent and vanishing after 60 min of incubation. In contrast, avirulent variants of C. burnetii did not induce any significant changes in cell morphology. The distribution of filamentous actin (F-actin) was then studied with a specific probe, bodipy phallacidin. Virulent C. burnetii induced a profound and transient reorganization of F-actin, accompanied by an increase in the F-actin content of THP-1 cells. F-actin was colocalized with myosin in cell protrusions, suggesting that actin polymerization and the tension of actin-myosin filaments play a role in C. burnetii-induced morphological changes. In addition, contact between the cell and the bacterium seems to be necessary to induce cytoskeleton reorganization. Bacterial supernatants did not stimulate actin remodeling, and virulent C. burnetii organisms were found in close apposition with F-actin protrusions. The manipulation of the actin cytoskeleton by C. burnetiimay therefore play a critical role in the internalization strategy of this bacterium.

scholarly journals Proline-rich transmembrane protein 2 (PRRT2) regulates the actin cytoskeleton during synaptogenesis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Elisa Savino ◽  
Romina Inès Cervigni ◽  
Miriana Povolo ◽  
Alessandra Stefanetti ◽  
Daniele Ferrante ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Neurotransmitter Release ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Transmembrane Protein ◽  
Neuronal Cell ◽  
Cell Aggregation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Filamentous Actin

Abstract Mutations in proline-rich transmembrane protein 2 (PRRT2) have been recently identified as the leading cause of a clinically heterogeneous group of neurological disorders sharing a paroxysmal nature, including paroxysmal kinesigenic dyskinesia and benign familial infantile seizures. To date, studies aimed at understanding its physiological functions in neurons have mainly focused on its ability to regulate neurotransmitter release and neuronal excitability. Here, we show that PRRT2 expression in non-neuronal cell lines inhibits cell motility and focal adhesion turnover, increases cell aggregation propensity, and promotes the protrusion of filopodia, all processes impinging on the actin cytoskeleton. In primary hippocampal neurons, PRRT2 silencing affects the synaptic content of filamentous actin and perturbs actin dynamics. This is accompanied by defects in the density and maturation of dendritic spines. We identified cofilin, an actin-binding protein abundantly expressed at the synaptic level, as the ultimate effector of PRRT2. Indeed, PRRT2 silencing unbalances cofilin activity leading to the formation of cofilin-actin rods along neurites. The expression of a cofilin phospho-mimetic mutant (cof-S3E) is able to rescue PRRT2-dependent defects in synapse density, spine number and morphology, but not the alterations observed in neurotransmitter release. Our data support a novel function of PRRT2 in the regulation of the synaptic actin cytoskeleton and in the formation of synaptic contacts.

scholarly journals CRMP-2 Is Involved in Kinesin-1-Dependent Transport of the Sra-1/WAVE1 Complex and Axon Formation

2005 ◽  
Vol 25 (22) ◽  
pp. 9920-9935 ◽  
Author(s):  
Yoji Kawano ◽  
Takeshi Yoshimura ◽  
Daisuke Tsuboi ◽  
Saeko Kawabata ◽  
Takako Kaneko-Kawano ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Hippocampal Neurons ◽  
Binding Proteins ◽  
Neuronal Development ◽  
Critical Role ◽  
Growth Cones ◽  
Axon Outgrowth ◽  
Actin Binding ◽  
Dependent Manner ◽  
Actin Binding Proteins

ABSTRACT A neuron has two types of highly polarized cell processes, the single axon and multiple dendrites. One of the fundamental questions of neurobiology is how neurons acquire such specific and polarized morphologies. During neuronal development, various actin-binding proteins regulate dynamics of actin cytoskeleton in the growth cones of developing axons. The regulation of actin cytoskeleton in the growth cones is thought to be involved in axon outgrowth and axon-dendrite specification. However, it is largely unknown which actin-binding proteins are involved in axon-dendrite specification and how they are transported into the developing axons. We have previously reported that collapsin response mediator protein 2 (CRMP-2) plays a critical role in axon outgrowth and axon-dendrite specification (N. Inagaki, K. Chihara, N. Arimura, C. Menager, Y. Kawano, N. Matsuo, T. Nishimura, M. Amano, and K. Kaibuchi, Nat. Neurosci. 4:781-782, 2001). Here, we found that CRMP-2 interacted with the specifically Rac1-associated protein 1 (Sra-1)/WASP family verprolin-homologous protein 1 (WAVE1) complex, which is a regulator of actin cytoskeleton. The knockdown of Sra-1 and WAVE1 by RNA interference canceled CRMP-2-induced axon outgrowth and multiple-axon formation in cultured hippocampal neurons. We also found that CRMP-2 interacted with the light chain of kinesin-1 and linked kinesin-1 to the Sra-1/WAVE1 complex. The knockdown of CRMP-2 and kinesin-1 delocalized Sra-1 and WAVE1 from the growth cones of axons. These results suggest that CRMP-2 transports the Sra-1/WAVE1 complex to axons in a kinesin-1-dependent manner and thereby regulates axon outgrowth and formation.

scholarly journals Polarization of gelsolin and actin binding protein in kidney epithelial cells.

1990 ◽  
Vol 38 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
J H Hartwig ◽  
D Brown ◽  
D A Ausiello ◽  
T P Stossel ◽  
L Orci
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Water Permeability ◽  
Collecting Duct ◽  
Regulatory Proteins ◽  
Actin Binding ◽  
Apical Plasma Membrane ◽  
Actin Binding Protein ◽  
Principal Cells ◽  
Actin Regulatory Proteins

Vasopressin regulates transepithelial osmotic water permeability in the kidney collecting duct and in target cells in other tissues. In the presence of hormone, water channels are inserted into an otherwise impermeable apical plasma membrane and the apical surface of these cells is dramatically remodelled. Because cytochalasin B and D greatly reduce the response of these cells to vasopressin, actin filaments are believed to participate in the events leading to an increase in transepithelial water permeability. Modulation of the actin filamentous network requires the concerted action of specific actin regulatory proteins, and in the present study we used protein A-gold immunocytochemistry to localize two important molecules, gelsolin and actin binding protein (ABP), in epithelial cells of the kidney inner medulla. Gelsolin and, to a lesser extent, ABP were concentrated in clusters in the apical cell web of principal cells of the collecting duct. Aggregates of gold particles were often associated with the cytoplasmic side of plasma membrane regions forming surface extensions or microvilli. The basolateral plasma membrane was labeled to a much lesser extent than the apical plasma membrane. In the thin limbs of Henle, ABP was localized over the apical plasma membrane in ascending limbs, but gelsolin labeling was weak in these cells. In thin descending limbs, the pattern of labeling was completely reversed, with abundant apical gelsolin labeling but only weak ABP immunolabeling. Although the significance of the distribution of actin regulatory proteins in thin limbs is unknown, the abundance and the predominantly apical polarization of both ABP and gelsolin in principal cells of the collecting duct is consistent with a role of the actin cytoskeleton in the mechanism of vasopressin actin.

scholarly journals Actin-binding proteins: the long road to understanding the dynamic landscape of cellular actin networks

2016 ◽  
Vol 27 (16) ◽  
pp. 2519-2522 ◽  
Author(s):  
Pekka Lappalainen
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Binding Proteins ◽  
Three Dimensional ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Binding Proteins ◽  
Vast Number ◽  
Actin Regulatory Proteins ◽  
The Individual

The actin cytoskeleton supports a vast number of cellular processes in nonmuscle cells. It is well established that the organization and dynamics of the actin cytoskeleton are controlled by a large array of actin-binding proteins. However, it was only 40 years ago that the first nonmuscle actin-binding protein, filamin, was identified and characterized. Filamin was shown to bind and cross-link actin filaments into higher-order structures and contribute to phagocytosis in macrophages. Subsequently many other nonmuscle actin-binding proteins were identified and characterized. These proteins regulate almost all steps of the actin filament assembly and disassembly cycles, as well as the arrangement of actin filaments into diverse three-dimensional structures. Although the individual biochemical activities of most actin-regulatory proteins are relatively well understood, knowledge of how these proteins function together in a common cytoplasm to control actin dynamics and architecture is only beginning to emerge. Furthermore, understanding how signaling pathways and mechanical cues control the activities of various actin-binding proteins in different cellular, developmental, and pathological processes will keep researchers busy for decades.

Histamine, actin-gelsolin binding, and polyphosphoinositides in human umbilical vein endothelial cells

1992 ◽  
Vol 263 (6) ◽  
pp. L664-L669 ◽  
Author(s):  
M. R. Carson ◽  
S. S. Shasby ◽  
S. E. Lind ◽  
D. M. Shasby
Keyword(s):  
Actin Cytoskeleton ◽  
Umbilical Vein ◽  
Phospholipid Metabolism ◽  
Actin Binding ◽  
Filamentous Actin ◽  
Human Umbilical Vein ◽  
Cell Calcium ◽  
Before And After ◽  
Inositol Phospholipid ◽  
Umbilical Vein Endothelial Cells

Histamine activates inositol phospholipid metabolism, increases calcium, and causes a change in shape of human umbilical vein endothelial (HUVE) cells. Changes in endothelial cell shape are determined, in part, by changes in the actin cytoskeleton. Gelsolin is an actin-binding protein with the potential to alter the actin cytoskeleton in response to changes in cell calcium and/or changes in polyphosphoinositides. Therefore, we examined the interactions of actin and gelsolin in HUVE cells in which inositol phospholipid metabolism was activated with histamine. In HUVE cells exposed to histamine we estimated actin-gelsolin binding by quantitating actin and gelsolin, immunoprecipitated with anti-gelsolin Sepharose. We estimated the relative amount of filamentous actin in the histamine-exposed HUVE cells by quantitating the amount of actin that was Triton soluble. We also measured the amount of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) in the HUVE cells before and after exposure to histamine. We found that histamine decreased the amount of actin that was immunoprecipitated with gelsolin, decreased the fraction of cell actin that was Triton soluble, and increased PIP and PIP2. These results demonstrate that histamine promotes actin filament formation in HUVE cells and that histamine-mediated changes in actin-gelsolin binding in these cells are better predicted by changes in polyphosphoinositides than by increases in cell calcium.

scholarly journals PakB binds to the SH3 domain of Dictyostelium Abp1 and regulates its effects on cell polarity and early development

2013 ◽  
Vol 24 (14) ◽  
pp. 2216-2227 ◽  
Author(s):  
Yidai Yang ◽  
Marc de la Roche ◽  
Scott W. Crawley ◽  
Zhihao Li ◽  
Emilia Furmaniak-Kazmierczak ◽  
...  
Keyword(s):  
Early Development ◽  
Actin Filaments ◽  
Cellular Localization ◽  
Critical Role ◽  
Leading Edge ◽  
Sh3 Domain ◽  
Cell Polarization ◽  
Actin Binding ◽  
Filamentous Actin ◽  
P21 Activated Kinase

Dictyostelium p21-activated kinase B (PakB) phosphorylates and activates class I myosins. PakB colocalizes with myosin I to actin-rich regions of the cell, including macropinocytic and phagocytic cups and the leading edge of migrating cells. Here we show that residues 1–180 mediate the cellular localization of PakB. Yeast two-hybrid and pull-down experiments identify two proline-rich motifs in PakB-1-180 that directly interact with the SH3 domain of Dictyostelium actin-binding protein 1 (dAbp1). dAbp1 colocalizes with PakB to actin-rich regions in the cell. The loss of dAbp1 does not affect the cellular distribution of PakB, whereas the loss of PakB causes dAbp1 to adopt a diffuse cytosolic distribution. Cosedimentation studies show that the N-terminal region of PakB (residues 1–70) binds directly to actin filaments, whereas dAbp1 exhibits only a low affinity for filamentous actin. PakB-1-180 significantly enhances the binding of dAbp1 to actin filaments. When overexpressed in PakB-null cells, dAbp1 completely blocks early development at the aggregation stage, prevents cell polarization, and significantly reduces chemotaxis rates. The inhibitory effects are abrogated by the introduction of a function-blocking mutation into the dAbp1 SH3 domain. We conclude that PakB plays a critical role in regulating the cellular functions of dAbp1, which are mediated largely by its SH3 domain.

scholarly journals Actin Cytoskeleton Role in the Maintenance of Neuronal Morphology and Long-Term Memory

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1795
Author(s):  
Raphael Lamprecht
Keyword(s):  
Actin Cytoskeleton ◽  
Neuronal Network ◽  
Morphological Changes ◽  
Neuronal Morphology ◽  
Regulatory Proteins ◽  
Long Term Memory ◽  
Term Memory ◽  
Actin Regulatory Proteins ◽  
Spine Structure

Evidence indicates that long-term memory formation creates long-lasting changes in neuronal morphology within a specific neuronal network that forms the memory trace. Dendritic spines, which include most of the excitatory synapses in excitatory neurons, are formed or eliminated by learning. These changes may be long-lasting and correlate with memory strength. Moreover, learning-induced changes in the morphology of existing spines can also contribute to the formation of the neuronal network that underlies memory. Altering spines morphology after memory consolidation can erase memory. These observations strongly suggest that learning-induced spines modifications can constitute the changes in synaptic connectivity within the neuronal network that form memory and that stabilization of this network maintains long-term memory. The formation and elimination of spines and other finer morphological changes in spines are mediated by the actin cytoskeleton. The actin cytoskeleton forms networks within the spine that support its structure. Therefore, it is believed that the actin cytoskeleton mediates spine morphogenesis induced by learning. Any long-lasting changes in the spine morphology induced by learning require the preservation of the spine actin cytoskeleton network to support and stabilize the spine new structure. However, the actin cytoskeleton is highly dynamic, and the turnover of actin and its regulatory proteins that determine and support the actin cytoskeleton network structure is relatively fast. Molecular models, suggested here, describe ways to overcome the dynamic nature of the actin cytoskeleton and the fast protein turnover and to support an enduring actin cytoskeleton network within the spines, spines stability and long-term memory. These models are based on long-lasting changes in actin regulatory proteins concentrations within the spine or the formation of a long-lasting scaffold and the ability for its recurring rebuilding within the spine. The persistence of the actin cytoskeleton network within the spine is suggested to support long-lasting spine structure and the maintenance of long-term memory.

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