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Related Experiment Videos

ProSAAS processing in mouse brain and pituitary.

N Mzhavia1, Y Berman, F Y Che

  • 1Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.

The Journal of Biological Chemistry
|November 30, 2000
PubMed
Summary
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ProSAAS protein processing in mice reveals major neuroendocrine peptides, little SAAS and big LEN. Impaired processing in Cpe(fat)/Cpe(fat) mice leads to partially processed peptides that may inhibit PC1 activity.

Area of Science:

  • Neuroendocrinology
  • Protein Biochemistry
  • Molecular Biology

Background:

  • ProSAAS is a newly identified protein with a neuroendocrine distribution similar to prohormone convertase 1 (PC1).
  • Previous studies identified proSAAS-derived peptides in Cpe(fat)/Cpe(fat) mice due to carboxypeptidase E (CPE) deficiency.
  • CPE is a crucial exopeptidase in peptide processing.

Purpose of the Study:

  • To investigate the processing profile of proSAAS in wild-type and Cpe(fat)/Cpe(fat) mouse tissues.
  • To identify the major proSAAS-derived peptides in mouse brain and pituitary.
  • To explore the potential functional roles of these peptides.

Main Methods:

  • Development of radioimmunoassays using antisera against different regions of proSAAS.

Related Experiment Videos

  • Analysis of proSAAS processing using gel filtration and reverse-phase high-performance liquid chromatography (RP-HPLC).
  • Mass spectrometry to confirm the identity and molecular masses of processed peptides.

    • Main Results:

    • In wild-type mice, proSAAS is extensively processed into smaller peptides, primarily little SAAS, PEN, and big LEN.
    • Mass spectrometry confirmed the presence of little SAAS and big LEN in mouse brain and pituitary fractions.
    • ProSAAS processing is slightly impaired in Cpe(fat)/Cpe(fat) mice, resulting in the accumulation of partially processed peptides, including a C-terminally extended form of PEN.

    Conclusions:

    • Little SAAS and big LEN are the major proSAAS-derived peptides produced in the mouse brain and pituitary.
    • The accumulation of partially processed PEN in Cpe(fat)/Cpe(fat) mice may inhibit PC1 activity, explaining reduced active PC1 levels.
    • These findings suggest that little SAAS and big LEN may function as neurotransmitters or hormones.