Distinct recycling of active and inactive β1 integrins

Antti Arjonen, Jonna Alanko, Stefan Veltel, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

174 Citations (Scopus)


Integrin trafficking plays an important role in cellular motility and cytokinesis. Integrins undergo constant endo/exocytic shuttling to facilitate the dynamic regulation of cell adhesion. Integrin activity toward the components of the extracellular matrix is regulated by the ability of these receptors to switch between active and inactive conformations. Several cellular signalling pathways have been described in the regulation of integrin traffic under different conditions. However, the interrelationship between integrin activity conformations and their endocytic fate have remained incompletely understood. Here, we have investigated the endocytic trafficking of active and inactive β1 integrins in cancer cells. Both conformers are endocytosed in a clathrin‐ and dynamin‐dependent manner. The net endocytosis rate of the active β1 integrins is higher, whereas endocytosis of the inactive β1 integrin is counteracted by rapid recycling back to the plasma membrane via an ARF6‐ and early endosome antigen 1‐positive compartment in an Rab4a‐ and actin‐dependent manner. Owing to these distinct trafficking routes, the two receptor pools display divergent subcellular localization. At steady state, the inactive β1 integrin is mainly on the plasma membrane, whereas the active receptor is predominantly intracellular. These data provide new insights into the endocytic traffic of integrins and imply the possibility of a previously unappreciated crosstalk between pathways regulating integrin activity and traffic.

Original languageEnglish
Pages (from-to)610-625
Issue number4
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed


This study was supported by Academy of Finland, ERC Starting Grant, Sigrid Juselius Foundation and Finnish Cancer Organizations. A. A. has been supported by V-S cultural foundation, Ida Montin foundation, Orion-Farmos foundation, Finnish Cancer Organizations, K. Albin Johanssons foundation and Instrumentarium foundation. S. V. has been supported by Feodor-Lynen programme of the Alexander von Humboldt foundation and EMBO long-term fellowship. A. A. is supported by the Turku Graduate School for Biomedical Sciences.


  • conformation
  • endocytosis
  • integrin
  • recycling
  • trafficking


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