Comparative binding of biotinylated neurotrophins to alpha(2)-macroglobulin family of proteins: relationship between cytokine-binding and neuro-modulatory activities of the macroglobulins.

Comparative binding of biotinylated neurotrophins to alpha(2)-macroglobulin family of proteins: relationship between cytokine-binding and neuro-modulatory activities of the macroglobulins.

Skornicka Erin L; Shi Xiaoqing; Koo Peter H

Journal of neuroscience research

2002

2002-02

Human alpha(2)-macroglobulin (alpha(2)M), pregnancy zone protein (PZP), rat alpha(1)M and acute-phase rat alpha(2)M belong to the alpha(2)M gene family of proteins, which can react covalently with nucleophilic monoamines to yield monoamine-activated (MA) macroglobulins. The MA forms of human alpha(2)M, PZP and rat alpha(2)M have been demonstrated previously to inhibit various neurotrophin-promoted neuronal activities, whereas MA-alpha(1)M is neurostimulatory and all native macroglobulins are generally inactive. The mechanism of neuromodulation is unknown, but it has been postulated that MA macroglobulins might inhibit neurons via their binding and sequestration of neurotrophins. This study employed a novel biotinylation-Western blot technique to compare the neurotrophin-binding properties of the four macroglobulins, and to correlate their binding activities with their known neuro-modulatory activities. In comparison with their respective native counterparts, human and rat

*Biotinylation; *Blotting; alpha-Macroglobulins/chemistry/*metabolism/pharmacology; Animals; Cytokines/chemistry/*metabolism; Humans; Iodine Radioisotopes/chemistry; Nerve Growth Factor/chemistry/metabolism; Nerve Growth Factors/chemistry/*metabolism; Neurons/drug effects; Pregnancy Proteins/chemistry/metabolism; Protein Binding/physiology; Rats; Species Specificity; Western

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