Binding of Gelsolin, a Secretory Protein, to Amyloid β-Protein

doi:10.1006/bbrc.1999.0623

Biochemical and Biophysical Research Communications

Volume 258, Issue 2, 10 May 1999, Pages 241-246

https://doi.org/10.1006/bbrc.1999.0623 Get rights and content

Abstract

Soluble amyloid β-protein (Aβ) is normally present in the cerebrospinal fluid (CSF) and plasma. However, it is fibrillized and deposited as plaques in the brains of patients with Alzheimer's disease. Cerebrospinal fluid (CSF) contains several circulating proteins (apolipoprotein E, apolipoprotein J, and transthyretin) that bind to Aβ. We report here that gelsolin, a secretory protein, also binds to Aβ in a concentration-dependent manner. Under similar conditions, other proteins such as G-actin, protein kinase C, polyglutamic acid, and gelatin did not bind to Aβ. Solid phase binding assays showed two Aβ binding sites on gelsolin that have dissociation constants (K_d) of 1.38 and 2.55 μM. Aβ was found to co-immunoprecipitate along with gelsolin from the plasma, suggesting that gelsolin–Aβ complex exists under physiological conditions. The gelsolin–Aβ complex was sodium dodecyl sulfate (SDS)stable in the absence of reducing agent, but was dissociated when the SDS stop solution contained dithiothreitol (reducing agent). This study suggests that the function of secretory gelsolin in the CSF and plasma is to bind and sequester Aβ.

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^☆: J. F. HoffmanG. Giebisch

¹: To whom correspondence should be addressed. Fax: 1-718-698-7916. E-mail:[email protected].

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Regular ArticleBinding of Gelsolin, a Secretory Protein, to Amyloid β-Protein☆

Abstract

Neuron

Arch. Biochem. Biophys.

J. Biol. Chem.

Neurosci. Lett.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Cell

Brain Res.

Neuroscience

Neurobiol. Aging

Brain Res.

J. Biol. Chem.

J. Biol. Chem.

Nature

Nature

Biochemistry

Proc. Natl. Acad. Sci. U.S.A.

Ann. Neurol.

Alzheimer's Res.

Proc. Natl. Acad. Sci. U.S.A.

Biochem. J.

Regular Article
Binding of Gelsolin, a Secretory Protein, to Amyloid β-Protein☆