The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development

Chikako Nakajima, Philipp Haffner, Sebastian M. Goerke, Kai Zurhove, Giselind Adelmann, Michael Frotscher, Joachim Herz, Hans H. Bock, Petra May

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migration. Our studies thus identify LRP1 as a novel player in angiogenesis and in the recruitment and maintenance of mural cells. Moreover, they reveal an unexpected link between lipoprotein receptor and sphingolipid signaling that, in addition to angiogenesis during embryonic development, is of potential importance for other targets of these pathways, such as tumor angiogenesis and inflammatory processes.

Original languageEnglish (US)
Pages (from-to)4513-4525
Number of pages13
JournalDevelopment (Cambridge)
Volume141
Issue number23
DOIs
StatePublished - Dec 1 2014

Fingerprint

Lipoprotein Receptors
Blood Vessels
Proteins
Embryonic Development
Low Density Lipoprotein Receptor-Related Protein-1
Sphingolipids
Cell Movement
Embryonic Structures
Maintenance
sphingosine 1-phosphate
Neoplasms

Keywords

  • Angiogenesis
  • Lipoprotein receptor
  • Sphingolipid

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Nakajima, C., Haffner, P., Goerke, S. M., Zurhove, K., Adelmann, G., Frotscher, M., ... May, P. (2014). The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development. Development (Cambridge), 141(23), 4513-4525. https://doi.org/10.1242/dev.109124

The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development. / Nakajima, Chikako; Haffner, Philipp; Goerke, Sebastian M.; Zurhove, Kai; Adelmann, Giselind; Frotscher, Michael; Herz, Joachim; Bock, Hans H.; May, Petra.

In: Development (Cambridge), Vol. 141, No. 23, 01.12.2014, p. 4513-4525.

Research output: Contribution to journalArticle

Nakajima, C, Haffner, P, Goerke, SM, Zurhove, K, Adelmann, G, Frotscher, M, Herz, J, Bock, HH & May, P 2014, 'The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development', Development (Cambridge), vol. 141, no. 23, pp. 4513-4525. https://doi.org/10.1242/dev.109124
Nakajima, Chikako ; Haffner, Philipp ; Goerke, Sebastian M. ; Zurhove, Kai ; Adelmann, Giselind ; Frotscher, Michael ; Herz, Joachim ; Bock, Hans H. ; May, Petra. / The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development. In: Development (Cambridge). 2014 ; Vol. 141, No. 23. pp. 4513-4525.
@article{4d6fa70be343483292c08df6dd569cb0,
title = "The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development",
abstract = "Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migration. Our studies thus identify LRP1 as a novel player in angiogenesis and in the recruitment and maintenance of mural cells. Moreover, they reveal an unexpected link between lipoprotein receptor and sphingolipid signaling that, in addition to angiogenesis during embryonic development, is of potential importance for other targets of these pathways, such as tumor angiogenesis and inflammatory processes.",
keywords = "Angiogenesis, Lipoprotein receptor, Sphingolipid",
author = "Chikako Nakajima and Philipp Haffner and Goerke, {Sebastian M.} and Kai Zurhove and Giselind Adelmann and Michael Frotscher and Joachim Herz and Bock, {Hans H.} and Petra May",
year = "2014",
month = "12",
day = "1",
doi = "10.1242/dev.109124",
language = "English (US)",
volume = "141",
pages = "4513--4525",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "23",

}

TY - JOUR

T1 - The lipoprotein receptor LRP1 modulates sphingosine-1-phosphate signaling and is essential for vascular development

AU - Nakajima, Chikako

AU - Haffner, Philipp

AU - Goerke, Sebastian M.

AU - Zurhove, Kai

AU - Adelmann, Giselind

AU - Frotscher, Michael

AU - Herz, Joachim

AU - Bock, Hans H.

AU - May, Petra

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migration. Our studies thus identify LRP1 as a novel player in angiogenesis and in the recruitment and maintenance of mural cells. Moreover, they reveal an unexpected link between lipoprotein receptor and sphingolipid signaling that, in addition to angiogenesis during embryonic development, is of potential importance for other targets of these pathways, such as tumor angiogenesis and inflammatory processes.

AB - Low density lipoprotein receptor-related protein 1 (LRP1) is indispensable for embryonic development. Comparing different genetically engineered mouse models, we found that expression of Lrp1 is essential in the embryo proper. Loss of LRP1 leads to lethal vascular defects with lack of proper investment with mural cells of both large and small vessels. We further demonstrate that LRP1 modulates Gi-dependent sphingosine-1-phosphate (S1P) signaling and integrates S1P and PDGF-BB signaling pathways, which are both crucial for mural cell recruitment, via its intracellular domain. Loss of LRP1 leads to a lack of S1P-dependent inhibition of RAC1 and loss of constraint of PDGF-BB-induced cell migration. Our studies thus identify LRP1 as a novel player in angiogenesis and in the recruitment and maintenance of mural cells. Moreover, they reveal an unexpected link between lipoprotein receptor and sphingolipid signaling that, in addition to angiogenesis during embryonic development, is of potential importance for other targets of these pathways, such as tumor angiogenesis and inflammatory processes.

KW - Angiogenesis

KW - Lipoprotein receptor

KW - Sphingolipid

UR - http://www.scopus.com/inward/record.url?scp=84911490417&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911490417&partnerID=8YFLogxK

U2 - 10.1242/dev.109124

DO - 10.1242/dev.109124

M3 - Article

VL - 141

SP - 4513

EP - 4525

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 23

ER -