GGA2 and RAB13 promote activity-dependent β1-integrin recycling

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Pranshu Sahgal1, Jonna Alanko1, Jaroslav Icha1

  • 1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku FIN-20520, Finland.

Journal of Cell Science
|May 12, 2019
PubMed

Insights

Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) and RAB13 regulate active β1-integrin recycling. Silencing these proteins reduces cancer cell migration and invasion by limiting active integrin levels.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • β1-integrins are crucial for cell-matrix interactions, influencing cell adhesion, migration, and cancer invasion.
  • The dynamic regulation of integrin trafficking is essential for these cellular processes.

Purpose of the Study:

  • To identify regulators of β1-integrin trafficking.
  • To investigate the role of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) and RAB GTPases in β1-integrin recycling and cancer cell behavior.

Main Methods:

  • RNA interference (RNAi) screen to identify integrin traffic regulators.
  • Proximity-dependent biotin identification (BioID) to discover protein interactors.
  • Assessment of β1-integrin levels in focal adhesions and cell migration/invasion assays.

Main Results:

  • GGA2 was identified as a regulator of active β1-integrin recycling.
  • Silencing GGA2 reduced active β1-integrin in focal adhesions, decreasing cancer cell migration and invasion.
  • RAB13 and RAB10 were identified as novel GGA2 interactors.
  • RAB13 silencing phenocopied GGA2 depletion, impairing active β1-integrin recycling and cell migration.

Conclusions:

  • GGA2 and RAB13 are key regulators of active β1-integrin recycling to the plasma membrane.
  • These proteins play critical roles in controlling integrin activity and are important for cancer cell migration and invasion.
  • GGA2 and RAB13 act as specificity determinants for integrin activity-dependent trafficking.
Keywords:
BioIDCargo adaptor proteinCell migrationGGA2Integrin trafficRAB13

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