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Structure-function studies on PEDF. A noninhibitory serpin with neurotrophic activity

S P Becerra1

  • 1Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2740, USA.

Advances in Experimental Medicine and Biology
|January 1, 1997
PubMed
Summary

Pigment Epithelium-Derived Factor (PEDF) exhibits neurotrophic functions, supporting neuronal differentiation and survival. Its structure reveals determinants for these non-inhibitory activities, suggesting a functional evolution of this serpin.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • The serpin, Pigment Epithelium-Derived Factor (PEDF), is present in the neural retina.
  • PEDF demonstrates neuronal differentiating and survival activities in vivo.
  • Its role as a neurotrophic factor is supported by its localization and functions.

Purpose of the Study:

  • To elucidate the structural determinants of PEDF's neurotrophic and non-inhibitory activities.
  • To understand the functional evolution of PEDF within the serpin superfamily.
  • To investigate the separation of inhibitory and specific activities in serpins.

Main Methods:

  • Structural analysis of PEDF.
  • Functional assays to determine neurotrophic activity.

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  • Comparative analysis with other serpins.

    • Main Results:

    • PEDF possesses characteristics of a serine protease substrate, not an inhibitor.
    • A specific N-terminus peptide region is crucial for PEDF's neurotrophic function.
    • Structural elements like signal peptide and oligosaccharides are dispensable for neurotrophic activity.

    Conclusions:

    • PEDF functions as a neurotrophic factor, distinct from typical serpin inhibitory roles.
    • Evolution may have led PEDF to lose inhibitory activity while gaining neurotrophic functions.
    • PEDF exemplifies the divergence of inhibitory and specific biological activities within the serpin family.