Distinct recycling of active and inactive β1 integrins
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Distinct recycling of active and inactive β1 integrins. / Arjonen, Antti; Alanko, Jonna; Veltel, Stefan; Ivaska, Johanna.
In: TRAFFIC, Vol. 13, No. 4, 01.04.2012, p. 610-25.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Distinct recycling of active and inactive β1 integrins
AU - Arjonen, Antti
AU - Alanko, Jonna
AU - Veltel, Stefan
AU - Ivaska, Johanna
N1 - © 2012 John Wiley & Sons A/S.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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.
KW - Antigens, CD29
KW - Cell Line, Tumor
KW - Endocytosis
KW - Flow Cytometry
KW - Humans
KW - Models, Biological
U2 - 10.1111/j.1600-0854.2012.01327.x
DO - 10.1111/j.1600-0854.2012.01327.x
M3 - SCORING: Journal article
C2 - 22222055
VL - 13
SP - 610
EP - 625
JO - TRAFFIC
JF - TRAFFIC
SN - 1398-9219
IS - 4
ER -