Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinases

I A Kramerova1, N Kawaguchi, L I Fessler

  • 1MCD Biology Department and Molecular Biology Institute, University of California at Los Angeles, CA 90095, USA.

Development (Cambridge, England)
|November 15, 2000
PubMed

Insights

Papilin, an extracellular matrix glycoprotein, plays a crucial role in embryonic development by influencing cell arrangements and modulating metalloproteinases. Its inhibition leads to developmental defects and embryonic lethality in model organisms.

Area of Science:

  • Developmental Biology
  • Extracellular Matrix Biology
  • Molecular Genetics

Background:

  • Papilin is an extracellular matrix glycoprotein identified in Drosophila, Caenorhabditis, and mammals.
  • Its conserved domain structure suggests functional links with metalloproteinases.
  • Papilin is found in various matrix structures during development, including basement membranes and hemocyte-associated matrices.

Purpose of the Study:

  • To elucidate the function of papilin in embryonic development.
  • To investigate the molecular interactions and mechanisms of papilin.
  • To determine the role of papilin in cell rearrangement and organogenesis.

Main Methods:

  • cDNA sequencing to identify papilin homologues.
  • In vitro biochemical assays to study enzyme inhibition.
  • Genetic manipulation (inhibition and ectopic expression) in Drosophila and Caenorhabditis.
  • Analysis of developmental defects and embryonic lethality.

Main Results:

  • Papilin's cDNA sequence revealed conserved domains, including a 'papilin cassette' shared with ADAMTS metalloproteinases.
  • Papilin non-competitively inhibits procollagen N-proteinase in vitro.
  • Inhibition of papilin synthesis resulted in defective cell arrangements and embryonic lethality.
  • Ectopic papilin expression caused lethal abnormalities in multiple organ systems.

Conclusions:

  • Papilin is essential for normal embryonic development, particularly for cell rearrangements.
  • Papilin likely modulates the activity of metalloproteinases during organogenesis.
  • Papilin's functions are conserved across different species, highlighting its fundamental biological importance.

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