ZFIN ID: ZDB-PUB-200701-26
GGA2 and RAB13 promote activity-dependent β1-integrin recycling
Sahgal, P., Alanko, J., Icha, J., Paatero, I., Hamidi, H., Arjonen, A., Pietilä, M., Rokka, A., Ivaska, J.
Date: 2019
Source: Journal of Cell Science   132(11): (Journal)
Registered Authors: Icha, Jaroslav, Ivaska, Johanna, Paatero, Ilkka
Keywords: BioID, Cargo adaptor protein, Cell migration, GGA2, Integrin traffic, RAB13
MeSH Terms:
  • Adaptor Proteins, Vesicular Transport/genetics
  • Adaptor Proteins, Vesicular Transport/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Breast Neoplasms/pathology*
  • Cell Adhesion/physiology
  • Cell Line, Tumor
  • Cell Movement/physiology*
  • Humans
  • Integrin beta1/metabolism*
  • Neoplasm Invasiveness/pathology
  • Neoplasm Transplantation
  • RNA Interference
  • RNA, Small Interfering/genetics
  • Transplantation, Heterologous
  • Zebrafish
  • rab GTP-Binding Proteins/genetics
  • rab GTP-Binding Proteins/metabolism*
PubMed: 31076515 Full text @ J. Cell Sci.
ABSTRACT
β1-integrins mediate cell-matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic.
ADDITIONAL INFORMATION