Full paper
Developmental patterns of gene expression of secreted proteins in brain and choroid plexus

https://doi.org/10.1016/0012-1606(89)90076-6Get rights and content

Abstract

The proteins secreted by the choroid plexus throughout rat brain development were analyzed by two-dimensional polyacrylamide gel electrophoresis following biosynthetic labeling of choroid plexus pieces with [14C]leucine in vitro. Approximately 20 major protein species were resolved which, with the exception of transferrin, transthyretin, and α2-macroglobulin, appear to be unrelated to proteins found in high concentrations in plasma. Several patterns of developmental regulation were observed. At least two of the proteins were synthesized and secreted at high levels only by fetal choroid plexus, whereas the secretion of several other proteins including transferrin and proteins comigrating with cystatin C and α2-macroglobulin increased only after birth. The levels of mRNA coding for transferrin, ceruloplasmin, cystatin C, α2-macroglobulin, β2-microglobulin, and transthyretin were measured in the brain during development by dot hybridization and northern gel analysis. No mRNA was detected coding for the proteins α-fetoprotein, α1-antitrypsin, haptoglobin, and thiostatin in the brain at any stage. For those proteins, which are produced in other parts of the brain as well as by the choroid plexus, the changes in their corresponding mRNA levels measured in whole brain paralleled the changes in their secretion by the choroid plexus. The results presented in this paper show that the choroid plexus is active in protein secretion at all stages studied. The changing pattern of protein secretion by the choroid plexus, combined with its early development compared with other tissues in the brain, suggests that it is active in providing the appropriate extracellular environment for the growth and differentiation of the brain.

References (57)

  • P.W. Dickson et al.

    Rat transthyretin (prealbumin): Molecular cloning, nucleotide sequence, and gene expression in the liver and brain

    J. Biol. Chem

    (1985)
  • P.W. Dickson et al.

    High levels of messenger RNA for transthyretin (prealbumin) in human choroid plexus

    Neurosci. Lett

    (1986)
  • K.M. Dziegielewska et al.

    Proteins in cerebrospinal fluid and plasma of fetal rats during development

    Dev. Biol

    (1981)
  • K.M. Dziegielewska et al.

    Synthesis of plasma proteins by rat fetal brain and choroid plexus

    Int. J. Dev. Neurosci

    (1984)
  • K.M. Dziegielewska et al.

    Messenger ribonucleic acid (mRNA) from developing rat cerebellum directs in vitro synthesis of plasma proteins

    Dev. Brain Res

    (1985)
  • W.-P. Fung et al.

    Structure and expression of the rat transthyretin (prealbumin) gene

    J. Biol. Chem

    (1988)
  • R.F. Keep et al.

    A morphometric analysis of the development of the fourth ventrical choroid plexus in the rat

    Dev. Brain Res

    (1986)
  • U.K. Laemmli et al.

    Maturation of the head of bacteriophage T4. I. DNA packaging events

    J. Mol. Biol

    (1973)
  • J.J. Latimer et al.

    Developmental expression, cellular localization and testosterone regulation of α1-antitrypsin in Mus caroli kidney

    J. Biol. Chem

    (1987)
  • M.J. Levin et al.

    Expression of the transferrin gene during development of non-hepatic tissues: High levels of transferrin mRNA in fetal muscle and adult brain

    Biochem. Biophys. Res. Commun

    (1984)
  • O.H. Lowry et al.

    Protein measurement with the Folin phenol reagent

    J. Biol. Chem

    (1951)
  • R.J. Mans et al.

    Measurement of the incorporation of radioactive amino acids into protein by a filter-paper disk method

    Arch. Biochem. Biophys

    (1961)
  • K. Mollgard et al.

    Synthesis and localization of plasma proteins in the developing human brain: Integrity of the fetal blood-brain barrier to endogenous proteins of hepatic origin

    Dev. Biol

    (1988)
  • W. Northemann et al.

    Molecular cloning of cDNA sequences for rat α2-macroglobulin and measurement of its transcription during experimental inflammation

    J. Biol. Chem

    (1985)
  • P.H. O'Farrell

    High resolution two-dimensional electrophoresis of proteins

    J. Biol. Chem

    (1975)
  • D.E. Panrucker et al.

    Acute phase α2-macroglobulin in CSF during development of the fetal rat

    Int. J. Dev. Neurosci

    (1983)
  • G.L. Peterson

    A simplification of the protein assay method of Lowry et al., which is more generally applicable

    Anal. Biochem

    (1977)
  • B.S. Schachter et al.

    Intraneuronal α-fetoprotein and albumin are not synthesized locally in developing brain

    Dev. Brain Res

    (1982)
  • Cited by (72)

    • Aluminum

      2012, Veterinary Toxicology: Basic and Clinical Principles
    • Functional roles of transferrin in the brain

      2012, Biochimica et Biophysica Acta - General Subjects
      Citation Excerpt :

      It is known that CSF flows into the four ventricles [74] and is in dynamic equilibrium with the interstitial fluid [75] thus providing a mechanism to disperse iron and Tf throughout the brain. Choroid plexus expresses Tf in vivo and has been shown to secrete Tf in vitro [76,77]. Iron can be taken up by the choroid plexus from the periphery [72] and reportedly enters the CSF at slow rates [71].

    • Aluminum

      2012, Veterinary Toxicology
    • Cystatins - Extra- and intracellular cysteine protease inhibitors: High-level secretion and uptake of cystatin C in human neuroblastoma cells

      2010, Biochimie
      Citation Excerpt :

      As for the other type 2 cystatins (with one exception), its gene is located in the cystatin multigene locus at chromosome 20 [13]. Cystatin C is produced in a wide variety of human tissues and cell lines [14,15] and it is the type 2 cystatin showing the most wide-spread body distribution. It is found in all body fluids at biologically significant concentrations and at particularly high levels in seminal plasma (∼50 mg/l or 3.7 μM) and cerebrospinal fluid (∼5.8 mg/l or 430 nM) [6].

    • Aluminum

      2007, Veterinary Toxicology: Basic and Clinical Principles
    • Aluminum

      2007, Veterinary Toxicology
    View all citing articles on Scopus
    View full text