Gelsolin is localized in neuronal growth cones

Tanaka, Junya; Kira, Masahiro; Sobue, Kenji

doi:10.1016/0165-3806(93)90217-x

Cited by 50 publications

(29 citation statements)

References 8 publications

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“…Overexpression of cytoplasmic gelsolin in NIH 3T3 fibroblasts enhances migration and wound healing in tissue culture (69). The high content of gelsolin in developing oligodendrocytes (70) and its localization in neuronal growth cones (71) are consistent with a role in motility. Gelsolin null mice have shown that, although not essential for motility during early embryogenesis, gelsolin is required for rapid motile responses in stressed cells involved in hemostasis, inflammation, and wound healing (72).…”

Section: Discussionmentioning

confidence: 71%

Evidence for Gelsolin as a Corneal Crystallin in Zebrafish

Kantorow

Davis

et al. 2000

Journal of Biological Chemistry

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We have shown that gelsolin is one of the most prevalent water-soluble proteins in the transparent cornea of zebrafish. There are also significant amounts of actin. In contrast to actin, gelsolin is barely detectable in other eye tissues (iris, lens, and remaining eye) of the zebrafish. Gelsolin cDNA hybridized intensely in Northern blots to RNA from the cornea but not from the lens, brain, or headless body. The deduced zebrafish gelsolin is ϳ60% identical to mammalian cytosolic gelsolin and has the characteristic six segmental repeats as well as the binding sites for actin, calcium, and phosphatidylinositides. In situ hybridization tests showed that gelsolin mRNA is concentrated in the zebrafish corneal epithelium. The zebrafish corneal epithelium stains very weakly with rhodamine-phalloidin, indicating little Factin in the cytoplasm. In contrast, the mouse corneal epithelium contains relatively little gelsolin and stains intensely with rhodamine-phalloidin, as does the zebrafish extraocular muscle. We propose, by analogy with the diverse crystallins of the eye lens and with the putative enzyme-crystallins (aldehyde dehydrogenase class 3 and other enzymes) of the mammalian cornea, that gelsolin and actin-gelsolin complexes act as watersoluble crystallins in the zebrafish cornea and contribute to its optical properties.Focused vision in the vertebrate eye depends upon light transmission through the transparent lens and cornea. The lens is an encapsulated tissue containing a layer of anterior, cuboidal epithelial cells and posterior, elongated fiber cells (1). By contrast, the transparent cornea has an anterior squamous epithelium comprising 5-7 cell layers overlying a relatively thick extracellular stroma containing ordered collagen fibers, proteoglycans, glycosaminoglycans, and keratocytes, and finally a posterior single layer of endothelial cells (2-5).The transparent and refractive properties of the eye lens depend upon the crystallins, which often differ among species in a taxon-specific fashion (6). The diverse crystallins comprise approximately 90% of the water-soluble proteins of the lens. Many lens crystallins are either closely related or identical to metabolic enzymes (the enzyme-crystallins) or stress proteins (small heat shock proteins) that are used outside of the lens for non-refractive purposes (7-9). The dual use of crystallins for metabolism and refraction has been called gene sharing (10).Because transparency of the cellular lens involves the intracellular crystallins (11-13), studies on corneal transparency have concentrated on the highly structured extracellular stroma (14, 15). However, corneal epithelial cells, like lens cells, contain unexpectedly high proportions of selected proteins (16 -19), raising the possibility that they may have structural roles related to transparency as do lens crystallins. Furthermore, these abundant intracellular corneal proteins are often enzymes, reminiscent of the enzyme-crystallins in the lens, suggesting that they are not serving strictly metabolic roles. ...

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Section: Discussionmentioning

confidence: 71%

Evidence for Gelsolin as a Corneal Crystallin in Zebrafish

Kantorow

Davis

et al. 2000

Journal of Biological Chemistry

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“…Our data suggest that actin depolymerization, effected by gelsolin, results in reduced C a 2ϩ influx through V DCC and NMDA receptor channels and may thereby play roles in modulating the kinds of calcium-dependent processes just described. Roles for gelsolin in regulating the responses of growth cones to signals that elevate [C a 2ϩ ] i are suggested from the presence of gelsolin in growth cones of developing neurons (Tanaka et al, 1993), data demonstrating that calcium and actin regulate growth cone motility (Lankford and Letourneau, 1989;Forscher et al, 1992), and the established role of gelsolin in mediating motility responses to Ca 2ϩ in non-neuronal cells (Hartwig and Kwiatkowski, 1991). However, it should be noted that there are no overt structural or functional alterations in the nervous systems of mice lacking gelsolin, indicating that gelsolin is not required for normal development of the nervous system.…”

Section: Discussionmentioning

confidence: 99%

“…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). Gelsolin is widely expressed in mammalian tissues including the nervous system (Kwiatkowski et al, 1988a,b); in the developing nervous system gelsolin is particularly concentrated in neuronal growth cones (Tanaka et al, 1993). Previous studies have shown that Ca 2ϩ influx, including that induced by membrane depolarization, can induce actin depolymerization in neurons (Bernstein and Bamburg, 1985;Furukawa et al, 1995), a process that likely involves gelsolin activity.…”

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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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“…Immunocytochemical studies using anti-gelsolin antibody revealed that the protein is localized in filopodia and the body part of growth cones of neuronally differentiated rat pheochromocytoma (PC12) cells treated with nerve growth factor (NGF) [31]. Gelsolin was also found in rat dorsal root ganglion neurons.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Alzheimer's amyloid-β peptide-induced reduction of mitochondrial membrane potential and neurotoxicity by gelsolin

Qiao¹,

Koya²,

Nakagawa³

et al. 2005

Neurobiology of Aging

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Amyloid-beta (Abeta) peptides play a central role in the development of Alzheimer's disease. They are known to induce mitochondrial dysfunction and caspase activation, resulting in apoptosis of neuronal cells. Here we show that human cytoplasmic gelsolin inhibits Abeta peptide-induced cell death of neuronally differentiated rat pheochromocytoma (PC-12) cells. We also show that the segment 5 but not 6 of human cytoplasmic gelsolin is the important region responsible for inhibition of Abeta-induced cytotoxicity. Mitochondrial dysfunction associated with cell death, membrane potential loss and the release of cytochrome c are all abrogated in the presence of human full-length or segment 5 cytoplasmic gelsolin. Furthermore, RNA interference to reduce expression of endogenous gelsolin in PC12 cells shows that rat gelsolin act as an inhibitor of Abeta cytotoxicity. These results demonstrate that cytoplasmic gelsolin plays a important role in inhibiting Abeta-induced cytotoxicity by inhibiting apoptotic mitochondrial changes. The segment 5 of human cytoplasmic gelsolin is sufficient for the function.

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Gelsolin is localized in neuronal growth cones

Cited by 50 publications

References 8 publications

Evidence for Gelsolin as a Corneal Crystallin in Zebrafish

Evidence for Gelsolin as a Corneal Crystallin in Zebrafish

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

Inhibition of Alzheimer's amyloid-β peptide-induced reduction of mitochondrial membrane potential and neurotoxicity by gelsolin

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