Home LiteratureArticle Details
PMID: 1330091 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells.

Molecular biology of the cell ·Vol. 3 ·No. 9 ·1992-09-00 ·Pages 1015-24

Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, Safer D, Nachmias VT, Pollard TD

Abstract

We present evidence for a new mechanism by which two major actin monomer binding proteins, thymosin beta 4 and profilin, may control the rate and the extent of actin polymerization in cells. Both proteins bind actin monomers transiently with a stoichiometry of 1:1. When bound to actin, thymosin beta 4 strongly inhibits the exchange of the nucleotide bound to actin by blocking its dissociation, while profilin catalytically promotes nucleotide exchange. Because both proteins exchange rapidly between actin molecules, low concentrations of profilin can overcome the inhibitory effects of high concentrations of thymosin beta 4 on the nucleotide exchange. These reactions may allow variations in profilin concentration (which may be regulated by membrane polyphosphoinositide metabolism) to control the ratio of ATP-actin to ADP-actin. Because ATP-actin subunits polymerize more readily than ADP-actin subunits, this ratio may play a key regulatory role in the assembly of cellular actin structures, particularly under circumstances of rapid filament turnover.

MeSH Terms
Actins/metabolism Adenosine/metabolism Adenosine Diphosphate/metabolism Adenosine Triphosphate/metabolism Binding, Competitive Blood Platelets/metabolism Contractile Proteins Humans Microfilament Proteins/metabolism Phosphatidylinositols/metabolism Profilins Thymosin/analogs & derivatives,metabolism
Chemicals
Actins Contractile Proteins Microfilament Proteins PFN1 protein, human Phosphatidylinositols Profilins thymosin beta(4) Thymosin Adenosine Diphosphate Adenosine Triphosphate Adenosine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Goldschmidt-Clermont P J
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Furman M I
Wachsstock D
Safer D
Nachmias V T
Pollard T D
References (50)
50 references, click to expand
  1. The kinetics of the exchange of G-actin-bound 1: N6-ethenoadenosine 5'-triphosphate with ATP as followed by fluorescence.
    Eur J Biochem. 1975 Sep 15;57(2):453-9 PMID: 240724
  2. Acanthamoeba profilin interacts with G-actin to increase the rate of exchange of actin-bound adenosine 5'-triphosphate.
    Biochemistry. 1980 Nov 11;19(23):5359-62 PMID: 6893804
  3. Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells.
    J Mol Biol. 1977 Sep 25;115(3):465-83 PMID: 563468
  4. Head to tail polymerization of actin.
    J Mol Biol. 1976 Nov;108(1):139-50 PMID: 1003481
  5. Kinetics of the cooperative association of actin to actin filaments.
    Biophys Chem. 1975 Jul;3(3):215-25 PMID: 1174645
  6. chickadee encodes a profilin required for intercellular cytoplasm transport during Drosophila oogenesis.
    Cell. 1992 Apr 3;69(1):173-84 PMID: 1339308
  7. Diacylglycerol-stimulated formation of actin nucleation sites at plasma membranes.
    Science. 1992 Apr 10;256(5054):245-7 PMID: 1373523
  8. Mechanism of the interaction of human platelet profilin with actin.
    J Cell Biol. 1991 Jun;113(5):1081-9 PMID: 1645736
  9. Profilin, a weak CAP for actin and RAS.
    Cell. 1991 Aug 9;66(3):419-21 PMID: 1651167
  10. Profilin-actin complexes directly elongate actin filaments at the barbed end.
    Biochemistry. 1992 Feb 18;31(6):1827-36 PMID: 1737036
  11. The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin.
    J Cell Biol. 1991 Dec;115(6):1621-8 PMID: 1757466
  12. Regulation of phospholipase C-gamma 1 by profilin and tyrosine phosphorylation.
    Science. 1991 Mar 8;251(4998):1231-3 PMID: 1848725
  13. Actin-binding proteins.
    Curr Opin Cell Biol. 1991 Feb;3(1):87-97 PMID: 1854489
  14. The GTPase superfamily: conserved structure and molecular mechanism.
    Nature. 1991 Jan 10;349(6305):117-27 PMID: 1898771
  15. Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase.
    Cell. 1991 Nov 15;67(4):701-16 PMID: 1934068
  16. The affinities of human platelet and Acanthamoeba profilin isoforms for polyphosphoinositides account for their relative abilities to inhibit phospholipase C.
    Cell Regul. 1990 Nov;1(12):937-50 PMID: 1966040
  17. Thymosin beta 4 and Fx, an actin-sequestering peptide, are indistinguishable.
    J Biol Chem. 1991 Mar 5;266(7):4029-32 PMID: 1999398
  18. The role of actin polymerization in cell motility.
    Annu Rev Physiol. 1991;53:585-605 PMID: 2042972
  19. Actin microfilament dynamics in locomoting cells.
    Nature. 1991 Jul 11;352(6331):126-31 PMID: 2067574
  20. The actin-binding protein profilin binds to PIP2 and inhibits its hydrolysis by phospholipase C.
    Science. 1990 Mar 30;247(4950):1575-8 PMID: 2157283
  21. Resemblance of actin-binding protein/actin gels to covalently crosslinked networks.
    Nature. 1990 May 3;345(6270):89-92 PMID: 2158633
  22. Actin.
    Curr Opin Cell Biol. 1990 Feb;2(1):33-40 PMID: 2183841
  23. Isolation of a 5-kilodalton actin-sequestering peptide from human blood platelets.
    Proc Natl Acad Sci U S A. 1990 Apr;87(7):2536-40 PMID: 2320573
  24. Expression of the thymosin beta 4 gene during differentiation of hematopoietic cells.
    Blood. 1990 Sep 1;76(5):977-84 PMID: 2393720
  25. Rapid induction of thymosin beta 4 in concanavalin A-stimulated thymocytes by translational control.
    J Biol Chem. 1990 Sep 15;265(26):15387-91 PMID: 2394730
  26. Purification of profilin from Saccharomyces cerevisiae and analysis of profilin-deficient cells.
    J Cell Biol. 1990 Jan;110(1):105-14 PMID: 2404021
  27. Acanthamoeba actin and profilin can be cross-linked between glutamic acid 364 of actin and lysine 115 of profilin.
    J Cell Biol. 1989 Aug;109(2):619-26 PMID: 2569469
  28. From signal to pseudopod. How cells control cytoplasmic actin assembly.
    J Biol Chem. 1989 Nov 5;264(31):18261-4 PMID: 2681192
  29. Association of profilin with filament-free regions of human leukocyte and platelet membranes and reversible membrane binding during platelet activation.
    J Cell Biol. 1989 Oct;109(4 Pt 1):1571-9 PMID: 2793934
  30. Kinetics of nucleotide and metal ion interaction with G-actin.
    Biochemistry. 1988 Mar 8;27(5):1785-92 PMID: 3365424
  31. Determination of thymosin beta 4 in human blood cells and serum.
    J Chromatogr. 1987 Jun 26;397:279-85 PMID: 3654821
  32. Actin polymerization and ATP hydrolysis.
    Science. 1987 Oct 30;238(4827):638-44 PMID: 3672117
  33. Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments.
    J Cell Biol. 1986 Dec;103(6 Pt 2):2747-54 PMID: 3793756
  34. Specific growth response of ras-transformed embryo fibroblasts to tumour promoters.
    Nature. 1985 Dec 5-11;318(6045):472-5 PMID: 4069218
  35. Measurement of protein by spectrophotometry at 205 nm.
    Anal Biochem. 1974 May;59(1):277-82 PMID: 4407487
  36. The interaction of bovine pancreatic deoxyribonuclease I and skeletal muscle actin.
    Eur J Biochem. 1980 Mar;104(2):367-79 PMID: 6244947
  37. Quantitative analysis of the effect of Acanthamoeba profilin on actin filament nucleation and elongation.
    Biochemistry. 1984 Dec 18;23(26):6631-41 PMID: 6543322
  38. Analysis of numerical methods for computer simulation of kinetic processes: development of KINSIM--a flexible, portable system.
    Anal Biochem. 1983 Apr 1;130(1):134-45 PMID: 6688159
  39. Actin from Thyone sperm assembles on only one end of an actin filament: a behavior regulated by profilin.
    J Cell Biol. 1983 Jul;97(1):112-24 PMID: 6863386
  40. Atomic structure of the actin:DNase I complex.
    Nature. 1990 Sep 6;347(6288):37-44 PMID: 2395459
  41. Oscillating actin polymerization/depolymerization responses in human polymorphonuclear leukocytes.
    J Biol Chem. 1989 Oct 5;264(28):16355-8 PMID: 2550438
  42. Role of nucleotide hydrolysis in the dynamics of actin filaments and microtubules.
    Int Rev Cytol. 1989;115:139-70 PMID: 2663760
  43. The hydrolysis of ATP that accompanies actin polymerization is essentially irreversible.
    FEBS Lett. 1988 Aug 1;235(1-2):211-4 PMID: 2969829
  44. Differential expression of the human thymosin-beta 4 gene in lymphocytes, macrophages, and granulocytes.
    J Immunol. 1987 Dec 1;139(11):3840-8 PMID: 3500230
  45. Nucleotide exchange between cytosolic ATP and F-actin-bound ADP may be a major energy-utilizing process in unstimulated platelets.
    Eur J Biochem. 1986 May 2;156(3):677-84 PMID: 3699030
  46. Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling.
    J Cell Biol. 1985 Aug;101(2):597-602 PMID: 4040521
  47. Opposite effects of cofilin and profilin from porcine brain on rate of exchange of actin-bound adenosine 5'-triphosphate.
    Biochemistry. 1985 Feb 26;24(5):1160-4 PMID: 4096896
  48. The critical concentration of actin in the presence of ATP increases with the number concentration of filaments and approaches the critical concentration of actin.ADP.
    J Biol Chem. 1984 May 25;259(10):6274-83 PMID: 6539330
  49. 12-fold difference between the critical monomer concentrations of the two ends of actin filaments in physiological salt conditions.
    Proc Natl Acad Sci U S A. 1983 Aug;80(16):4922-5 PMID: 6576365
  50. Exchange of ADP, ATP and 1: N6-ethenoadenosine 5'-triphosphate at G-actin. Equilibrium and kinetics.
    Eur J Biochem. 1979 Nov 1;101(1):163-9 PMID: 510301
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.3.9.1015
Published
1992-09-00
Pages
1015-24
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC275662
Subset
IM
Grants
NIAMS NIH HHS · AR-40840 · United States
NIGMS NIH HHS · GM-26338 · United States
External Links
PubMed source DOI: 10.1091/mbc.3.9.1015 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2