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EGF-mediated Golgi dynamics and cell migration require CARP2.

Rahul Sharma1, Krishanu Dey Das1, Srinivasa M Srinivasula1

  • 1School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Maruthamala PO, Vithura, Thiruvananthapuram 695551, Kerala, India.

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|October 23, 2024
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Summary
This summary is machine-generated.

Caspase-8- and caspase-10-associated RING-containing protein 2 (CARP2) regulates Golgi dynamics by targeting Golgin45 for degradation. This reveals a link between endosomal ubiquitin signaling and Golgi architecture maintenance.

Keywords:
CP: Cell biology

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Area of Science:

  • Cell Biology
  • Molecular Biology

Background:

  • Mammalian cells feature a dynamic Golgi ribbon architecture essential for cellular function.
  • Disruptions in Golgi structure are implicated in diseases like cancer and neurodegeneration.
  • Regulators of Golgi dynamics remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of CARP2 (caspase-8- and caspase-10-associated RING-containing protein 2) in modulating Golgi dynamics.
  • To elucidate the mechanism by which CARP2 influences Golgi architecture.

Main Methods:

  • Utilized mammalian cell culture models.
  • Investigated the effects of epidermal growth factor (EGF) stimulation on CARP2 levels and Golgi morphology.
  • Employed CARP2 knockout (KO) cells and CARP2 variants with defects in endosomal association or ligase activity.
  • Analyzed Golgin45 ubiquitination and degradation.

Main Results:

  • EGF treatment increased CARP2 protein levels and induced Golgi dispersal.
  • Exogenous CARP2 also caused Golgi dispersal.
  • CARP2 KO cells maintained Golgi integrity upon EGF treatment.
  • CARP2 variants lacking endosomal association or ligase activity failed to disperse the Golgi.
  • CARP2 was shown to ubiquitinate and degrade Golgin45 in EGF-stimulated cells.

Conclusions:

  • CARP2 is a novel regulator of Golgi dynamics.
  • CARP2 mediates Golgi dispersal through its ubiquitin ligase activity and endosomal association.
  • CARP2's mechanism involves the ubiquitination and degradation of Golgin45.
  • This study uncovers a crosstalk between endosomal ubiquitin signaling and Golgi dynamics.