Abstract
The nerve growth factor protein (NGF) favors polymerization of brain actin and induces its organization to form paracrystalline structures that activate myosin ATPase (ATP phosphohydrolase, EC 3.6.1.3) to an extent greater than actin alone. Binding studies show that the initial 1:1 stoichiometry of NGF-G-actin complexes decreases to 1:7-10 when polymerization is ended and paracrystalline structures are formed. The ratio becomes even lower when heavy meromyosin is added in the absence of ATP, suggesting that heavy meromyosin displaces NGF bound to actin microfilaments. This conclusion is supported by the finding that when heavy meromyosin is added to NGF-microfilament complexes, under conditions for "decorating" microfilaments, the usual paracrystalline structure of the complexes disappears. The NGF-mediated organization of actin and activation of myosin ATPase is visualized as a self-regulatory and self-propagating mechanism, because progressive displacement of the growth factor induced by heavy meromyosin binding to F actin as ATP consumption proceeds renders an increasingly higher amount of NGF free for new interactions. These findings are discussed in the light of the mechanism of action of NGF in the target cells.
MeSH Terms
Actins/metabolism
Actomyosin/metabolism
Adenosine Triphosphatases/metabolism
Binding Sites
Brain/metabolism
Cytoskeleton/metabolism,ultrastructure
Enzyme Activation/drug effects
Myosin Subfragments/metabolism
Myosins/metabolism
Nerve Growth Factors/pharmacology
Protein Binding
Chemicals
Actins
Myosin Subfragments
Nerve Growth Factors
Actomyosin
Adenosine Triphosphatases
Myosins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Calissano P
Monaco G
Castellani L
Mercanti D
Levi A
References (19)
19 references, click to expand
-
ELECTRON MICROSCOPE STUDIES ON THE STRUCTURE OF NATURAL AND SYNTHETIC PROTEIN FILAMENTS FROM STRIATED MUSCLE.
J Mol Biol. 1963 Sep;7:281-308
PMID: 14064165
-
Interaction of nerve growth factor with tubulin. Studies on binding and induced polymerization.
Biochim Biophys Acta. 1975 Jul 14;399(1):50-60
PMID: 238651
-
Nerve growth factor prevents vinblastine destructive effects on sympathetic ganglia in newborn mice.
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5559-63
PMID: 271981
-
Substructure of the myosin molecule. I. Subfragments of myosin by enzymic degradation.
J Mol Biol. 1969 May 28;42(1):1-29
PMID: 4241282
-
Actin activation of heavy meromyosin adenosine triphosphatase. Dependence on adenosine triphosphate and actin concentrations.
J Biol Chem. 1970 May 10;245(9):2451-6
PMID: 4245608
-
Interaction of monomeric and polymeric actin with myosin subfragment 1.
J Mol Biol. 1972 May 28;66(3):435-44
PMID: 4260956
-
Muscular contraction and cell motility.
Nature. 1973 Jun 22;243(5408):445-9
PMID: 4275580
-
Ultrastructure and function of growth cones and axons of cultured nerve cells.
J Cell Biol. 1971 Jun;49(3):614-35
PMID: 4326456
-
Actomyosin-like protein in brain.
Science. 1973 Feb 2;179(4072):441-6
PMID: 4350213
-
Properties of the beta nerve growth factor receptor of avian dorsal root ganglia.
Proc Natl Acad Sci U S A. 1973 Dec;70(12):3884-8
PMID: 4359493
-
Isolation and quantitation of Ntau-methylhistidine in actin and myosin of rat skeletal muscle: use of pyridine elution of protein hydrolysates on ion-exchange resins.
Biochim Biophys Acta. 1974 Nov 5;371(1):226-37
PMID: 4429719
-
Binding of nerve growth factor receptor in sympathetic ganglia.
Proc Natl Acad Sci U S A. 1973 Sep;70(9):2519-23
PMID: 4517666
-
Interaction of nerve growth factor with the mouse-brain neurotubule protein(s).
Proc Natl Acad Sci U S A. 1974 May;71(5):2131-5
PMID: 4525323
-
Muscle-like contractile proteins and tubulin in synaptosomes.
Proc Natl Acad Sci U S A. 1974 Nov;71(11):4472-6
PMID: 4530997
-
Role of contractile microfilaments in macrophage movement and endocytosis.
Nat New Biol. 1971 Aug 4;232(31):153-5
PMID: 4937093
-
The nerve growth factor: purification as a 30,000-molecular-weight protein.
Proc Natl Acad Sci U S A. 1969 Oct;64(2):787-94
PMID: 4982360
-
In vitro effects of the nerve growth factor on the fine structure of the sensory nerve cells.
Brain Res. 1968 May;8(2):347-62
PMID: 5652725
-
Effect of NGF on in vitro preformed microtubules. Evidence for a protective action against vinblastine.
Brain Res. 1977 Jul 1;129(2):265-74
PMID: 884504
-
Unpolymerized actin in fibroblasts and brain.
J Mol Biol. 1976 Aug 25;105(4):527-44
PMID: 987247