Premium
Comparative binding of biotinylated neurotrophins to α 2 ‐macroglobulin family of proteins: Relationship between cytokine‐binding and neuro‐modulatory activities of the macroglobulins
Author(s) -
Skornicka Erin L.,
Shi Xiaoqing,
Koo Peter H.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10097
Subject(s) - macroglobulin , neurite , neurotrophin , monoamine neurotransmitter , chemistry , ciliary neurotrophic factor , biology , microbiology and biotechnology , biochemistry , neurotrophic factors , serotonin , in vitro , receptor
Human α 2 ‐macroglobulin (α 2 M), pregnancy zone protein (PZP), rat α 1 M and acute‐phase rat α 2 M belong to the α 2 M gene family of proteins, which can react covalently with nucleophilic monoamines to yield monoamine‐activated (MA) macroglobulins. The MA forms of human α 2 M, PZP and rat α 2 M have been demonstrated previously to inhibit various neurotrophin‐promoted neuronal activities, whereas MA‐α 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 MA‐α 2 M bound slightly more NGF, but significantly less BDNF or NT‐3. Native human α 2 M and PZP in general have no neuro‐modulatory activity, but native PZP bound significantly more NGF, BDNF or NT‐3 than either native α 2 M or MA‐α 2 M, which is neuro‐inhibitory. It is known that MA‐PZP is neuro‐inhibitory, but it fails to bind more NGF, BDNF, or NT‐3 than native PZP. MA‐α 1 M is the only macroglobulin known to stimulate NGF‐promoted neurite outgrowth, but it bound NGF with similar affinities as native α 1 M and rat α 2 M; in addition, it bound significantly less BDNF or NT‐3 than native α 1 M. All the bindings were non‐covalent and appeared specific. In conclusion, PZP and rat macroglobulins are versatile carriers of neurotrophins with diverse binding capacities, and the neurotrophin‐binding property does not appear to mediate the neuro‐modulatory activity of these human and rat macroglobulins. © 2002 Wiley‐Liss, Inc.