Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST

Hongyun Nie1, Yueyue Liu1, Xiaolei Yin2

  • 1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Shandong University School of Life Sciences, Jinan, Shandong 250100, China.

Neural Plasticity
|November 22, 2016
PubMed

Insights

The protein PIST retains Protocadherin 15 (PCDH15) in the Golgi, reducing its membrane expression. This finding reveals PIST

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Protocadherin 15 (PCDH15) is essential for inner ear hair cell function and hearing.
  • Mutations in the PCDH15 gene are linked to various forms of hearing loss.
  • Mechanisms controlling PCDH15 intracellular transport are not well understood.

Purpose of the Study:

  • To investigate the role of PIST in the intracellular trafficking of PCDH15.
  • To elucidate the interaction between PIST and PCDH15.
  • To understand how PIST affects PCDH15 membrane expression.

Main Methods:

  • Co-immunoprecipitation assays to confirm PIST-PCDH15 interaction.
  • Analysis of protein localization using immunofluorescence microscopy.
  • Assessment of membrane protein expression levels.

Main Results:

  • PIST directly interacts with PCDH15 via its PDZ domain and PCDH15's C-terminal PDZ-binding interface.
  • PIST retains PCDH15 within the trans-Golgi network (TGN).
  • PIST reduces the surface membrane expression of PCDH15.

Conclusions:

  • PIST acts as a regulator of PCDH15 intracellular transport.
  • PIST influences the membrane targeting of PCDH15, impacting hair cell function.
  • PIST also regulates the membrane expression of CDH23, suggesting a broader role in tip-link protein trafficking.

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