Topological assignment of the N-terminal extension of plasma gelsolin to the gelsolin surface

Fock, Ulrike; Jockusch, Brigitte M.; Schubert, Wolf‐Dieter; Hinssen, Horst

doi:10.1042/bj20040875

Cited by 6 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to different functions of plasma and cytoplasmic gelsolins [ 16 , 20 ], differentiation of these isoforms is crucial for proper validation of clinical utility. The use of monoclonal antibodies recognizing exclusively the extracellular isoform of GSN, or primers that flank unique sequences of plasma gelsolin would be a good approach, although one that has only been sparsely employed [ 193 , 194 ].…”

Section: Alterations In Plasma Gelsolin Concentrations In Differenmentioning

confidence: 99%

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Piktel

Levental

Durnaś

et al. 2018

IJMS

113

View full text Add to dashboard Cite

Gelsolin, an actin-depolymerizing protein expressed both in extracellular fluids and in the cytoplasm of a majority of human cells, has been recently implicated in a variety of both physiological and pathological processes. Its extracellular isoform, called plasma gelsolin (pGSN), is present in blood, cerebrospinal fluid, milk, urine, and other extracellular fluids. This isoform has been recognized as a potential biomarker of inflammatory-associated medical conditions, allowing for the prediction of illness severity, recovery, efficacy of treatment, and clinical outcome. A compelling number of animal studies also demonstrate a broad spectrum of beneficial effects mediated by gelsolin, suggesting therapeutic utility for extracellular recombinant gelsolin. In the review, we summarize the current data related to the potential of pGSN as an inflammatory predictor and therapeutic target, discuss gelsolin-mediated mechanisms of action, and highlight recent progress in the clinical use of pGSN.

show abstract

Section: Alterations In Plasma Gelsolin Concentrations In Differenmentioning

confidence: 99%

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Piktel

Levental

Durnaś

et al. 2018

IJMS

113

View full text Add to dashboard Cite

show abstract

“…Alternative splicing is frequently observed in the 5'‐untranslated regions, suggesting possible differences in transcription control, associated mRNA binding proteins, and mRNA localization. Alternative splicing in the protein‐coding regions is most common within the N‐terminal extension, which is proposed to bind loosely to the surface of gelsolin [Fock et al, ]. Isoform g lacks the B and C' strands and the start of the C strand from G1 which removes the G1 type‐2 calcium binding site and two actin‐binding residues (Fig.…”

Section: Gelsolin Isoformsmentioning

confidence: 99%

Gelsolin: The tail of a molecular gymnast

et al. 2013

View full text Add to dashboard Cite

Gelsolin superfamily members are Ca 21 -dependent, multidomain regulators of the actin cytoskeleton. Calcium binding activates gelsolin by inducing molecular gymnastics (large-scale conformational changes) that expose actin interaction surfaces by releasing a series of latches. A specialized tail latch has distinguished gelsolin within the superfamily. Active gelsolin exhibits actin filament severing and capping, and actin monomer sequestering activities. Here, we analyze a combination of sequence, structural, biophysical and biochemical data to assess whether the molecular plasticity, regulation and actinrelated properties of gelsolin are also present in other superfamily members. We conclude that all members of the superfamily will be able to transition between a compact conformation and a more open form, and that most of these open forms will interact with actin. Supervillin, which lacks the severing domain 1 and the F-actin binding-site on domain 2, is the clear exception. Eight calcium-binding sites are absolutely conserved in gelsolin, adseverin, advillin and villin, and compromised to increasing degrees in CapG, villin-like protein, supervillin and flightless I. Advillin, villin and supervillin each contain a potential tail latch, which is absent from CapG, adseverin and flightless I, and ambiguous in villin-like protein. Thus, calcium regulation will vary across the superfamily. Potential novel isoforms of the superfamily suggest complex regulation at the gene, transcript and protein levels. We review animal, clinical and cellular data that illuminate how the regulation of molecular flexibility in gelsolin-like proteins permits cells to exploit the force generated from actin polymerization to drive processes such as cell movement in health and disease. V C 2013 Wiley Periodicals, Inc.

show abstract

“…tested in extracellular space using an antibody specific only to its secreted isoform. This fact suggests the possibility that cytoplasmic gelsolin released from damaged or dying cells interferes with measurements of the concentration and activity of plasma gelsolin [68,69]. To address this issue, some studies evaluated the presence of gelsolin in blood parallel to the presence of actin as a measure of cell damage [64].…”

Section: A the Function Of Gelsolin In Extracellular Fluids Is Largementioning

confidence: 99%

Plasma Gelsolin: Function, Prognostic Value, and Potential Therapeutic Use

Bucki¹,

Levental²,

Kułakowska³

et al. 2008

CPPS

View full text Add to dashboard Cite

Gelsolin is a highly conserved, multifunctional actin-binding protein initially described in the cytosol of macrophages and subsequently identified in many vertebrate cells. A unique property of gelsolin is that in addition to its widely recognized function as a cytoplasmic regulator of actin organization, the same gene expresses a splice variant coding for a distinct isoform, plasma gelsolin, which is secreted into extracellular fluids. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulating enzymes. Consistent with these proposed functions, blood gelsolin levels decrease markedly in a variety of clinical conditions such as acute respiratory distress syndrome, sepsis, major trauma, prolonged hyperoxia, malaria, and liver injury. This correlation between blood gelsolin levels and critical clinical conditions suggests the potential utility of gelsolin as a prognostic marker as well as the possibility for therapeutic replenishment of gelsolin to alleviate the injurious cascades in these settings. This review summarizes current data supporting a role of plasma gelsolin in extracellular fluids and the potential for its use as a diagnostic marker or therapeutic treatment in several medical conditions.

show abstract

Topological assignment of the N-terminal extension of plasma gelsolin to the gelsolin surface

Cited by 6 publications

References 37 publications

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Plasma Gelsolin: Indicator of Inflammation and Its Potential as a Diagnostic Tool and Therapeutic Target

Gelsolin: The tail of a molecular gymnast

Plasma Gelsolin: Function, Prognostic Value, and Potential Therapeutic Use

Contact Info

Product

Resources

About