VEGFR1 (Flt1) Regulates Rab4 Recycling to Control Fibronectin Polymerization and Endothelial Vessel Branching

Matthew C. Jones; Patrick T. Caswell; K Moran‐Jones; Marnie Roberts; Simon T. Barry; Alexandra Gampel; Harry Mellor; Jim C. Norman

doi:10.1111/j.1600-0854.2009.00898.x

VEGFR1 (Flt1) Regulates Rab4 Recycling to Control Fibronectin Polymerization and Endothelial Vessel Branching

Matthew C. Jones, Patrick T. Caswell, K Moran‐Jones, Marnie Roberts, Simon T. Barry, Alexandra Gampel, Harry Mellor, Jim C. Norman^*

^*Corresponding author for this work

Peninsula Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

The cell's main receptor for VEGF, VEGFR2 (Kdr) is one of the most important positive regulators of new blood vessel growth and its downstream signalling is well characterized. By contrast, VEGFR1 (Flt1) and the mechanisms by which this VEGF receptor promotes branching morphogenesis in angiogenesis remain relatively unclear. Here we report that engagement of VEGFR1 activates a Rab4A‐dependent pathway that transports αvβ3 integrin from early endosomes to the plasma membrane, and that this is required for VEGF‐driven fibronectin polymerization in endothelial cells. Furthermore, VEGFR1 acts to promote endothelial tubule branching in an organotypic model of angiogenesis via a mechanism that requires Rab4A and αvβ3 integrin. We conclude that a recycling pathway regulated by Rab4A is a critical effector of VEGFR1 during branching morphogenesis of the vasculature.

Original language	English
Pages (from-to)	754-766
Number of pages	0
Journal	Traffic
Volume	10
Issue number	6
Early online date	15 May 2009
DOIs	https://doi.org/10.1111/j.1600-0854.2009.00898.x
Publication status	Published - Jun 2009

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title = "VEGFR1 (Flt1) Regulates Rab4 Recycling to Control Fibronectin Polymerization and Endothelial Vessel Branching",

abstract = " The cell's main receptor for VEGF, VEGFR2 (Kdr) is one of the most important positive regulators of new blood vessel growth and its downstream signalling is well characterized. By contrast, VEGFR1 (Flt1) and the mechanisms by which this VEGF receptor promotes branching morphogenesis in angiogenesis remain relatively unclear. Here we report that engagement of VEGFR1 activates a Rab4A‐dependent pathway that transports αvβ3 integrin from early endosomes to the plasma membrane, and that this is required for VEGF‐driven fibronectin polymerization in endothelial cells. Furthermore, VEGFR1 acts to promote endothelial tubule branching in an organotypic model of angiogenesis via a mechanism that requires Rab4A and αvβ3 integrin. We conclude that a recycling pathway regulated by Rab4A is a critical effector of VEGFR1 during branching morphogenesis of the vasculature. ",

author = "Jones, {Matthew C.} and Caswell, {Patrick T.} and K Moran‐Jones and Marnie Roberts and Barry, {Simon T.} and Alexandra Gampel and Harry Mellor and Norman, {Jim C.}",

year = "2009",

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doi = "10.1111/j.1600-0854.2009.00898.x",

language = "English",

volume = "10",

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T1 - VEGFR1 (Flt1) Regulates Rab4 Recycling to Control Fibronectin Polymerization and Endothelial Vessel Branching

AU - Jones, Matthew C.

AU - Caswell, Patrick T.

AU - Moran‐Jones, K

AU - Roberts, Marnie

AU - Barry, Simon T.

AU - Gampel, Alexandra

AU - Mellor, Harry

AU - Norman, Jim C.

PY - 2009/6

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N2 - The cell's main receptor for VEGF, VEGFR2 (Kdr) is one of the most important positive regulators of new blood vessel growth and its downstream signalling is well characterized. By contrast, VEGFR1 (Flt1) and the mechanisms by which this VEGF receptor promotes branching morphogenesis in angiogenesis remain relatively unclear. Here we report that engagement of VEGFR1 activates a Rab4A‐dependent pathway that transports αvβ3 integrin from early endosomes to the plasma membrane, and that this is required for VEGF‐driven fibronectin polymerization in endothelial cells. Furthermore, VEGFR1 acts to promote endothelial tubule branching in an organotypic model of angiogenesis via a mechanism that requires Rab4A and αvβ3 integrin. We conclude that a recycling pathway regulated by Rab4A is a critical effector of VEGFR1 during branching morphogenesis of the vasculature.

AB - The cell's main receptor for VEGF, VEGFR2 (Kdr) is one of the most important positive regulators of new blood vessel growth and its downstream signalling is well characterized. By contrast, VEGFR1 (Flt1) and the mechanisms by which this VEGF receptor promotes branching morphogenesis in angiogenesis remain relatively unclear. Here we report that engagement of VEGFR1 activates a Rab4A‐dependent pathway that transports αvβ3 integrin from early endosomes to the plasma membrane, and that this is required for VEGF‐driven fibronectin polymerization in endothelial cells. Furthermore, VEGFR1 acts to promote endothelial tubule branching in an organotypic model of angiogenesis via a mechanism that requires Rab4A and αvβ3 integrin. We conclude that a recycling pathway regulated by Rab4A is a critical effector of VEGFR1 during branching morphogenesis of the vasculature.

U2 - 10.1111/j.1600-0854.2009.00898.x

DO - 10.1111/j.1600-0854.2009.00898.x

M3 - Article

SN - 1398-9219

VL - 10

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EP - 766

JO - Traffic

JF - Traffic

IS - 6

ER -

VEGFR1 (Flt1) Regulates Rab4 Recycling to Control Fibronectin Polymerization and Endothelial Vessel Branching

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