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Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay
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Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

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Arrestin is required for agonist-induced trafficking of voltage-dependent calcium channels

Akil Puckerin1, Lanying Liu, Natasha Permaul

  • 1Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.

The Journal of Biological Chemistry
|August 17, 2006
PubMed

Insights

Voltage-dependent calcium channels rapidly internalize upon metabotropic receptor activation. This study reveals voltage-dependent calcium channels pre-associate with arrestin, facilitating rapid neuronal trafficking and suggesting a new role for arrestin.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Metabotropic receptors in the nervous system inhibit voltage-dependent calcium channels via signaling pathways.
  • Seven-transmembrane receptor activation triggers rapid calcium channel internalization (within seconds).

Purpose of the Study:

  • To investigate the mechanism behind the rapid internalization of voltage-dependent calcium channels upon receptor activation.
  • To determine if the endocytic machinery is closely associated with calcium channels for swift internalization.

Main Methods:

  • Investigated the association between voltage-dependent calcium channels and arrestin.
  • Examined the role of arrestin in GABAB receptor-mediated calcium channel internalization.
  • Utilized peptides to disrupt arrestin-channel binding and assess effects on internalization.

Main Results:

  • Voltage-dependent calcium channels are pre-associated with arrestin, a known protein in receptor trafficking.
  • GABAB receptor activation leads to the recruitment of receptors to the arrestin-channel complex and subsequent internalization.
  • beta-Arrestin 1 selectively binds to the SNARE-binding region of the calcium channel.
  • Peptides targeting the arrestin-binding site inhibit agonist-induced channel internalization.

Conclusions:

  • Voltage-dependent calcium channels form pre-assembled complexes with arrestin.
  • Arrestin plays a crucial role in the rapid, agonist-induced internalization of neuronal calcium channels.
  • These findings suggest a novel function for arrestin in neuronal signaling and trafficking.

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