Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration
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Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. / Mai, Anja; Veltel, Stefan; Pellinen, Teijo; Padzik, Artur; Coffey, Eleanor; Marjomäki, Varpu; Ivaska, Johanna.
in: J CELL BIOL, Jahrgang 194, Nr. 2, 25.07.2011, S. 291-306.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration
AU - Mai, Anja
AU - Veltel, Stefan
AU - Pellinen, Teijo
AU - Padzik, Artur
AU - Coffey, Eleanor
AU - Marjomäki, Varpu
AU - Ivaska, Johanna
PY - 2011/7/25
Y1 - 2011/7/25
N2 - Integrin trafficking from and to the plasma membrane controls many aspects of cell behavior including cell motility, invasion, and cytokinesis. Recruitment of integrin cargo to the endocytic machinery is regulated by the small GTPase Rab21, but the detailed molecular mechanisms underlying integrin cargo recruitment are yet unknown. Here we identify an important role for p120RasGAP (RASA1) in the recycling of endocytosed α/β1-integrin heterodimers to the plasma membrane. Silencing of p120RasGAP attenuated integrin recycling and augmented cell motility. Mechanistically, p120RasGAP interacted with the cytoplasmic domain of integrin α-subunits via its GAP domain and competed with Rab21 for binding to endocytosed integrins. This in turn facilitated exit of the integrin from Rab21- and EEA1-positive endosomes to drive recycling. Our results assign an unexpected role for p120RasGAP in the regulation of integrin traffic in cancer cells and reveal a new concept of competitive binding of Rab GTPases and GAP proteins to receptors as a regulatory mechanism in trafficking.
AB - Integrin trafficking from and to the plasma membrane controls many aspects of cell behavior including cell motility, invasion, and cytokinesis. Recruitment of integrin cargo to the endocytic machinery is regulated by the small GTPase Rab21, but the detailed molecular mechanisms underlying integrin cargo recruitment are yet unknown. Here we identify an important role for p120RasGAP (RASA1) in the recycling of endocytosed α/β1-integrin heterodimers to the plasma membrane. Silencing of p120RasGAP attenuated integrin recycling and augmented cell motility. Mechanistically, p120RasGAP interacted with the cytoplasmic domain of integrin α-subunits via its GAP domain and competed with Rab21 for binding to endocytosed integrins. This in turn facilitated exit of the integrin from Rab21- and EEA1-positive endosomes to drive recycling. Our results assign an unexpected role for p120RasGAP in the regulation of integrin traffic in cancer cells and reveal a new concept of competitive binding of Rab GTPases and GAP proteins to receptors as a regulatory mechanism in trafficking.
KW - Animals
KW - Binding, Competitive
KW - Cell Line, Tumor
KW - Cell Membrane
KW - Cell Movement
KW - Cytoplasm
KW - Endosomes
KW - Humans
KW - Integrins
KW - Mice
KW - Models, Biological
KW - Protein Binding
KW - Protein Structure, Tertiary
KW - Vesicular Transport Proteins
KW - p120 GTPase Activating Protein
KW - rab GTP-Binding Proteins
U2 - 10.1083/jcb.201012126
DO - 10.1083/jcb.201012126
M3 - SCORING: Journal article
C2 - 21768288
VL - 194
SP - 291
EP - 306
JO - J CELL BIOL
JF - J CELL BIOL
SN - 0021-9525
IS - 2
ER -