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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, Vol. 194, No. 2, 25.07.2011, p. 291-306.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mai, A, Veltel, S, Pellinen, T, Padzik, A, Coffey, E, Marjomäki, V & Ivaska, J 2011, 'Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration', J CELL BIOL, vol. 194, no. 2, pp. 291-306. https://doi.org/10.1083/jcb.201012126

APA

Mai, A., Veltel, S., Pellinen, T., Padzik, A., Coffey, E., Marjomäki, V., & Ivaska, J. (2011). Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. J CELL BIOL, 194(2), 291-306. https://doi.org/10.1083/jcb.201012126

Vancouver

Mai A, Veltel S, Pellinen T, Padzik A, Coffey E, Marjomäki V et al. Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. J CELL BIOL. 2011 Jul 25;194(2):291-306. https://doi.org/10.1083/jcb.201012126

Bibtex

@article{bd6cc0a479004ac18f666f2315a4f1fa,
title = "Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration",
abstract = "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.",
keywords = "Animals, Binding, Competitive, Cell Line, Tumor, Cell Membrane, Cell Movement, Cytoplasm, Endosomes, Humans, Integrins, Mice, Models, Biological, Protein Binding, Protein Structure, Tertiary, Vesicular Transport Proteins, p120 GTPase Activating Protein, rab GTP-Binding Proteins",
author = "Anja Mai and Stefan Veltel and Teijo Pellinen and Artur Padzik and Eleanor Coffey and Varpu Marjom{\"a}ki and Johanna Ivaska",
year = "2011",
month = jul,
day = "25",
doi = "10.1083/jcb.201012126",
language = "English",
volume = "194",
pages = "291--306",
journal = "J CELL BIOL",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

RIS

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 -