Search tips
Search criteria 


Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1988 February 1; 106(2): 375–384.
PMCID: PMC2114988

Genomic organization and biosynthesis of secreted and cytoplasmic forms of gelsolin


Gelsolin is an actin regulatory protein which is unique among vertebrates in that it is found as both an intrinsic cytoplasmic protein and as a secreted plasma protein. We demonstrate that plasma and cytoplasmic gelsolins are derived by alternative transcriptional initiation sites and message processing from a single gene 70 kb long, containing at least 14 exons. Their message and amino acid sequences are identical except at the 5' end/NH2 termini. The cytoplasmic- specific 5' sequence is derived from two exons that encode untranslated sequence, while the plasma message-specific 5' sequence is derived from a single exon that encodes untranslated sequence, the signal peptide, and the first 21 residues of the plasma protein. The two transcriptional initiation sites are separated by greater than or equal to 32 kb. Biosynthetic and RNase protection studies indicate that a number of cell types make both plasma and cytoplasmic gelsolin in widely varying amounts and ratios.

Full Text

The Full Text of this article is available as a PDF (1.9M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aviv H, Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. [PubMed]
  • Breathnach R, Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. [PubMed]
  • Breitbart RE, Andreadis A, Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. [PubMed]
  • Bryan J, Coluccio LM. Kinetic analysis of F-actin depolymerization in the presence of platelet gelsolin and gelsolin-actin complexes. J Cell Biol. 1985 Oct;101(4):1236–1244. [PMC free article] [PubMed]
  • Bryan J, Kurth MC. Actin-gelsolin interactions. Evidence for two actin-binding sites. J Biol Chem. 1984 Jun 25;259(12):7480–7487. [PubMed]
  • Carlson M, Taussig R, Kustu S, Botstein D. The secreted form of invertase in Saccharomyces cerevisiae is synthesized from mRNA encoding a signal sequence. Mol Cell Biol. 1983 Mar;3(3):439–447. [PMC free article] [PubMed]
  • Carron CP, Hwo SY, Dingus J, Benson DM, Meza I, Bryan J. A re-evaluation of cytoplasmic gelsolin localization. J Cell Biol. 1986 Jan;102(1):237–245. [PMC free article] [PubMed]
  • Chaponnier C, Borgia R, Rungger-Brändle E, Weil R, Gabbiani G. An actin-destabilizing factor is present in human plasma. Experientia. 1979 Aug 15;35(8):1039–1041. [PubMed]
  • Chaponnier C, Yin HL, Stossel TP. Reversibility of gelsolin/actin interaction in macrophages. Evidence of Ca2+-dependent and Ca2+-independent pathways. J Exp Med. 1987 Jan 1;165(1):97–106. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Cole FS, Schneeberger EE, Lichtenberg NA, Colten HR. Complement biosynthesis in human breast-milk macrophages and blood monocytes. Immunology. 1982 Jun;46(2):429–441. [PubMed]
  • Dale RM, McClure BA, Houchins JP. A rapid single-stranded cloning strategy for producing a sequential series of overlapping clones for use in DNA sequencing: application to sequencing the corn mitochondrial 18 S rDNA. Plasmid. 1985 Jan;13(1):31–40. [PubMed]
  • Dynan WS, Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. Nature. 316(6031):774–778. [PubMed]
  • Ginsburg D, Handin RI, Bonthron DT, Donlon TA, Bruns GA, Latt SA, Orkin SH. Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization. Science. 1985 Jun 21;228(4706):1401–1406. [PubMed]
  • Goldring SR, Mahaffey JE, Rosenblatt M, Dayer JM, Potts JT, Jr, Krane SM. Parathyroid hormone inhibitors: comparison of biological activity in bone- and skin-derived tissue. J Clin Endocrinol Metab. 1979 Apr;48(4):655–659. [PubMed]
  • Harris HE, Bamburg JR, Weeds AG. Actin filament disassembly in blood plasma. FEBS Lett. 1980 Nov 17;121(1):175–177. [PubMed]
  • Janmey PA, Stossel TP. Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate. Nature. 1987 Jan 22;325(6102):362–364. [PubMed]
  • Janmey PA, Chaponnier C, Lind SE, Zaner KS, Stossel TP, Yin HL. Interactions of gelsolin and gelsolin-actin complexes with actin. Effects of calcium on actin nucleation, filament severing, and end blocking. Biochemistry. 1985 Jul 2;24(14):3714–3723. [PubMed]
  • Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. [PMC free article] [PubMed]
  • Kwiatkowski DJ, Stossel TP, Orkin SH, Mole JE, Colten HR, Yin HL. Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain. Nature. 1986 Oct 2;323(6087):455–458. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. [PubMed]
  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. [PMC free article] [PubMed]
  • Ng SY, Gunning P, Eddy R, Ponte P, Leavitt J, Shows T, Kedes L. Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Mol Cell Biol. 1985 Oct;5(10):2720–2732. [PMC free article] [PubMed]
  • Nodes BR, Shackelford JE, Lebherz HG. Synthesis and secretion of serum gelsolin by smooth muscle tissue. J Biol Chem. 1987 Apr 15;262(11):5422–5427. [PubMed]
  • Norberg R, Thorstensson R, Utter G, Fagraeus A. F-Actin-depolymerizing activity of human serum. Eur J Biochem. 1979 Oct 15;100(2):575–583. [PubMed]
  • Osborne TF, Goldstein JL, Brown MS. 5' end of HMG CoA reductase gene contains sequences responsible for cholesterol-mediated inhibition of transcription. Cell. 1985 Aug;42(1):203–212. [PubMed]
  • Perlman D, Halvorson HO. Distinct repressible mRNAs for cytoplasmic and secreted yeast invertase are encoded by a single gene. Cell. 1981 Aug;25(2):525–536. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Smith DB, Janmey PA, Herbert TJ, Lind SE. Quantitative measurement of plasma gelsolin and its incorporation into fibrin clots. J Lab Clin Med. 1987 Aug;110(2):189–195. [PubMed]
  • Stossel TP, Chaponnier C, Ezzell RM, Hartwig JH, Janmey PA, Kwiatkowski DJ, Lind SE, Smith DB, Southwick FS, Yin HL, et al. Nonmuscle actin-binding proteins. Annu Rev Cell Biol. 1985;1:353–402. [PubMed]
  • Weeds AG, Gooch J, Pope B, Harris HE. Preparation and characterization of pig plasma and platelet gelsolins. Eur J Biochem. 1986 Nov 17;161(1):69–76. [PubMed]
  • Yin HL, Stossel TP. Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium-dependent regulatory protein. Nature. 1979 Oct 18;281(5732):583–586. [PubMed]
  • Yin HL, Stossel TP. Purification and structural properties of gelsolin, a Ca2+-activated regulatory protein of macrophages. J Biol Chem. 1980 Oct 10;255(19):9490–9493. [PubMed]
  • Yin HL, Albrecht JH, Fattoum A. Identification of gelsolin, a Ca2+-dependent regulatory protein of actin gel-sol transformation, and its intracellular distribution in a variety of cells and tissues. J Cell Biol. 1981 Dec;91(3 Pt 1):901–906. [PMC free article] [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press