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Novel Insights into NDP52 Autophagy Receptor Functioning

Christophe Viret1, Aurore Rozières1, Mathias Faure1

  • 1CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France; INSERM, U1111, Lyon, France; CNRS, UMR5308, Lyon, France; Ecole Normale Supérieure de Lyon, Lyon, France; Université Lyon 1, Centre International de Recherche en Infectiologie, 21 Av T. Garnier, 69007 Lyon, France; Equipe labellisée Fondation pour la Recherche Médicale FRM, France.

Trends in Cell Biology
|February 4, 2018
PubMed

Insights

Nuclear dot protein 52 (NDP52) is crucial for selective autophagy, guiding targets to autophagosomes and promoting their fusion with endolysosomes. Rab35 GTPase and MYOSIN VI (MYO6) are key regulators in this process.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Selective autophagy is a vital cellular process for degrading specific cargo.
  • Nuclear dot protein 52 (NDP52/CALCOCO2) is known to play a role in autophagy.
  • The precise mechanisms by which NDP52 functions and its regulation are still under investigation.

Purpose of the Study:

  • To elucidate the multifaceted roles of NDP52 in selective autophagy.
  • To investigate the involvement of Rab35 GTPase and MYOSIN VI (MYO6) in NDP52-mediated autophagy.
  • To understand how NDP52 regulates cargo targeting and autophagosome-endolysosome fusion.

Main Methods:

  • Immunoprecipitation assays to study protein interactions.
  • Confocal microscopy to visualize NDP52 localization and cargo.
  • Biochemical assays to analyze autophagosome-endolysosome fusion.
  • Studies involving Rab35 GTPase and MYOSIN VI (MYO6) manipulation.

Main Results:

  • NDP52 interacts with both autophagy targets and LC3, directing them to autophagosomes.
  • NDP52 facilitates autophagosome-endolysosome fusion by linking autophagosomes to MYOSIN VI (MYO6).
  • Rab35 GTPase regulates the recruitment of NDP52 to its targets, and NDP52 triggers MYOSIN VI (MYO6) motility.

Conclusions:

  • NDP52 is a key mediator in selective autophagy, involved in both cargo recognition and autophagosome maturation.
  • The interplay between NDP52, Rab35 GTPase, and MYOSIN VI (MYO6) is critical for efficient autophagic flux.
  • These findings provide new insights into the molecular machinery governing selective autophagy.
Keywords:
NDP52autophagosomeautophagy receptormaturationmyosin VIselective autophagy

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