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CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis

Xènia Crespo-Yàñez1, Carmen Aguilar-Gurrieri1,2, Anne-Claire Jacomin1

  • 1Institut de Biosciences et Biotechnologies de Grenoble (BIG), Univ. Grenoble Alpes, INSERM U1038, CEA, Grenoble, France.

Plos Genetics
|June 23, 2018
PubMed

Insights

The ESCRT-III protein CHMP1B is dynamically ubiquitinated during epidermal growth factor (EGF) signaling, a process crucial for EGF receptor trafficking and development. Ubiquitin-specific protease 8 (USP8) deubiquitinates CHMP1B, facilitating its function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Regulation

Background:

  • Plasma membrane receptor endocytosis and sorting are vital for cellular signaling.
  • The Endosomal Sorting Complex-III (ESCRT-III) machinery regulates membrane dynamics during endosomal sorting.
  • Multivesicular bodies (MVBs) mediate the sorting of receptors to lysosomes or recycling pathways.

Purpose of the Study:

  • To investigate the role of ubiquitination in the function of the ESCRT-III component CHMP1B.
  • To identify the enzymes involved in the ubiquitination and deubiquitination of CHMP1B.
  • To elucidate the impact of CHMP1B ubiquitination on cellular processes like receptor trafficking and development.

Main Methods:

  • Biochemical assays to detect ubiquitination and deubiquitination of CHMP1B.
  • Co-immunoprecipitation to identify interacting proteins within CHMP1B complexes.
  • Cellular assays using human cells and Drosophila models to assess CHMP1B function in EGF receptor trafficking and wing development.

Main Results:

  • CHMP1B is ubiquitinated on a flexible loop and deubiquitinated by USP8.
  • EGF stimulation leads to transient accumulation of ubiquitinated CHMP1B on cell membranes.
  • CHMP1B ubiquitination is essential for EGF receptor trafficking and Drosophila wing development.

Conclusions:

  • CHMP1B ubiquitination is a dynamic regulatory mechanism in response to EGF signaling.
  • USP8-mediated deubiquitination of CHMP1B may promote its assembly into functional ESCRT-III polymers.
  • This regulation is critical for proper receptor trafficking and developmental processes.

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