Partial purification and characterization of an actin depolymerizing factor from brain

Bamburg, James R.; Harris, Harriet E.; Weeds, Alan G.

doi:10.1016/0014-5793(80)81292-0

Cited by 204 publications

(125 citation statements)

References 14 publications

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“…In the fibroblast, a progression of cytoskeletal arrangements is seen from the newly polymerized actin network at the leading edge (Wang, 1985), to the production of "arcs" (Heath, 1983) composed of small bundles of filaments which are continually swept towards the nucleus where an arrangement oflarger perinuclear actin bundles known as the cellular geodome is found . As actophorin-like proteins (Mabuchi, 1983;Bamburg et al, 1980) and gelsolin (another actin filament severing protein), have been isolated from a number of vertebrate sources, it is possible that severing activity in concert with crosslinking proteins also found in protruding lamella (Geiger et al, 1984) form an increasingly anisotropic gel by a mechanism similar to that postulated here.…”

Section: Physiological Relevance Of These Findingsmentioning

confidence: 67%

The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin.

Maciver

Wachsstock

Schwarz

et al. 1991

The Journal of Cell Biology

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Abstract. The actin filament severing protein, Acanthamoeba actophorin, decreases the viscosity of actin filaments, but increases the stiffness and viscosity of mixtures of actin filaments and the crosslinking protein a-actinin . The explanation of this paradox is that in the presence of both the severing protein and crosslinker the actin filaments aggregate into an interlocking meshwork of bundles large enough to be visualized by light microscopy. The size of these bundles depends on the size of the containing vessel . The actin filaments in these bundles are tightly packed in some areas while in others they are more disperse. The bundles form a continuous reticulum that fills the container, since the filaments from a particular bundle S NCE the first descriptions of ameboid locomotion a century and a half ago, the concept of a reversible transformation between "sol" and "gel" has been central to hypothesis attempting to explain the phenomenon. Although it was proposed that the protoplasm is a contractile three-dimensional reticulum as early as 1873 (De Bruyn, 1947), only in comparatively recent times has this reticulum been shown to be mainly an actin-based system (Pollard and Ito, 1970) . Subsequent research has revealed that cytoplasmic actin filaments are associated with myosin (reviewed by Korn and Hammer, 1988) and a number of other proteins that regulate actin filament assembly and crosslinking (reviewed by Stossel et al., 1985, andPollard and . Because there are multiple crosslinking proteins in these cytoplasmic actin gels, the physiological function of the individual crosslinking proteins by mutation or gene disruption is difficult to demonstrate (Wallraff et al ., 1986;Schleicher et al., 1988). Consequently most of our knowledge about cytoplasmic actin gels has come from in vitro reconstitution with actin and purified individual crosslinkers such as a-actinin.Alpha-actinin is a major actin crosslinking protein in skeletal muscle and nonmuscle cells . Skeletal muscle a-actinins are calcium-insensitive crosslinking proteins. Some, but not all, a-actinins from smooth muscle and nonmuscle cells are inhibited by calcium . Acanthamoeba a-actinin is calcium insensitive but is otherwise a typical a-actinin (Pollard, 1981;

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Section: Physiological Relevance Of These Findingsmentioning

confidence: 67%

The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin.

Maciver

Wachsstock

Schwarz

et al. 1991

The Journal of Cell Biology

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“…ADF was originally purified from chick brain and found to increase the actin monomer pool (Bamburg et al 1980). Cofilin was purified from porcine brain and increased the actin monomer pool, but also bound F-actin monomers with a 1 : 1 stoichiometry (Maekawa et al 1984).…”

Section: Rho Gtpases: Organizers Of Actin Structuresmentioning

confidence: 99%

Signaling mechanisms that regulate actin‐based motility processes in the nervous system

Meyer

Feldman

2002

Journal of Neurochemistry

172

108

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Actin-based motility is critical for nervous system development. Both the migration of neurons and the extension of neurites require organized actin polymerization to push the cell membrane forward. Numerous extracellular stimulants of motility and axon guidance cues regulate actin-based motility through the rho GTPases (rho, rac, and cdc42). The rho GTPases reorganize the actin cytoskeleton, leading to stress fiber, filopodium, or lamellipodium formation. The activity of the rho GTPases is regulated by a variety of proteins that either stimulate GTP uptake (activation) or hydrolysis (inactivation). These proteins potentially link extracellular signals to the activation state of rho GTPases. Effectors downstream of the rho GTPases that directly influence actin polymerization have been identified and are involved in neurite development.The Arp2/3 complex nucleates the formation of new actin branches that extend the membrane forward. Ena/VASP proteins can cause the formation of longer actin filaments, characteristic of growth cone actin morphology, by preventing the capping of barbed ends. Actin-depolymerizing factor (ADF)/cofilin depolymerizes and severs actin branches in older parts of the actin meshwork, freeing monomers to be re-incorporated into actively growing filaments. The signaling mechanisms by which extracellular cues that guide axons to their targets lead to direct effects on actin filament dynamics are becoming better understood. Keywords: actin-depolymerizing factor (ADF)/cofilin, actinrelated protein Arp2/3, ena/VASP, LIM kinase, rho GTPase.

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“…The absence of overt alterations in brain development of GϪ/Ϫ mice, and the normal appearance of GϪ/Ϫ hippocampal neurons in culture suggested the possibility that there may be compensatory changes in the levels of other actin-binding proteins such as those in the actin-depolymerizing factor (ADF)-cofilin family (Bamburg et al, 1980;Hayden et al, 1993;Abe et al, 1996;Lappalainen and Drubin, 1997), or in levels of actin itself, in the GϪ/Ϫ mice. Moreover, actin-binding proteins in the ADF-cofilin family can inhibit binding of phalloidin to actin.…”

Section: Reduced Actin Depolymerization In Response To Calcium Influxmentioning

confidence: 99%

“…One broad class of proteins with F-actin binding and severing activity includes gelsolin (Yin and Stossel, 1979;Yin et al, 1981a), villin (Bretscher and Weber, 1980), and adseverin (Maekawa et al, 1989). Another class of actin-binding proteins that bind actin monomers and exhibit relatively weak actin-severing activity includes actin-depolymerizing factor (Bamburg et al, 1980;Morgan et al, 1993) and cofilin (Yonezawa et al, 1985). Gelsolin is a 93 kDa cytosolic protein that severs actin filaments when it is activated by Ca 2ϩ ; after cleaving actin filaments, gelsolin remains tightly bound to the actin filament barbed end (Yin et al, 1981b;Cooper et al, 1987;Janmey and Stossel, 1987).…”

mentioning

confidence: 99%

The Actin-Severing Protein Gelsolin Modulates Calcium Channel and NMDA Receptor Activities and Vulnerability to Excitotoxicity in Hippocampal Neurons

et al. 1997

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Calcium influx through NMDA receptors and voltagedependent calcium channels (VDCC) mediates an array of physiological processes in neurons and may also contribute to neuronal degeneration and death in neurodegenerative conditions such as stroke and severe epileptic seizures. Gelsolin is a Ca 2ϩ -activated actin-severing protein that is expressed in neurons, wherein it may mediate motility responses to Ca 2ϩ influx. Primary hippocampal neurons cultured from mice lacking gelsolin exhibited decreased actin filament depolymerization and enhanced Ca 2ϩ influx after exposure to glutamate. Whole-cell patch-clamp analyses showed that currents through NMDA receptors and VDCC were enhanced in hippocampal neurons lacking gelsolin, as a result of decreased current rundown; kainate-induced currents were similar in neurons containing and lacking gelsolin. Vulnerability of cultured hippocampal neurons to glutamate toxicity was greater in cells lacking gelsolin. Seizure-induced damage to hippocampal pyramidal neurons was exacerbated in adult gelsolin-deficient mice. These findings identify novel roles for gelsolin in controlling actinmediated feedback regulation of Ca 2ϩ influx and in neuronal injury responses. The data further suggest roles for gelsolin and the actin cytoskeleton in both physiological and pathophysiological events that involve activation of NMDA receptors and VDCC.

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Partial purification and characterization of an actin depolymerizing factor from brain

Cited by 204 publications

References 14 publications

The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin.

The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin.

Signaling mechanisms that regulate actin‐based motility processes in the nervous system

The Actin-Severing Protein Gelsolin Modulates Calcium Channel and NMDA Receptor Activities and Vulnerability to Excitotoxicity in Hippocampal Neurons

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