PUBLICATION

GIPC proteins negatively modulate Plexind1 signaling during vascular development

Authors
Carretero-Ortega, J., Chhangawala, Z., Hunt, S., Narvaez, C., Menéndez-González, J., Gay, C.M., Zygmunt, T., Li, X., Torres-Vázquez, J.
ID
ZDB-PUB-190507-27
Date
2019
Source
eLIFE   8: (Journal)
Registered Authors
Carretero-Ortega, Jorge, Chhangawala, Zinal, Gay, Carl Michael, Hunt, Shane, Narvaez, Carlos, Zygmunt, Tomasz
Keywords
GIPC, PlexinD1, Zebrafish, angiogenesis, cell signaling, developmental biology, zebrafish
MeSH Terms
  • Neovascularization, Physiologic*
  • Animals
  • Endothelial Cells/enzymology*
  • Endothelial Cells/physiology*
  • Carrier Proteins/metabolism*
  • Semaphorins/metabolism
  • Zebrafish Proteins/metabolism*
  • Receptors, Cell Surface/metabolism*
  • Signal Transduction*
  • Zebrafish
  • Protein Binding
(all 11)
PubMed
31050647 Full text @ Elife
Abstract
Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular communication. SEMA-PLXND1 signaling plays important roles in cardiovascular, nervous, and immune system development, and cancer biology. However, little is known about the molecular mechanisms that modulate SEMA-PLXND1 signaling. As PLXND1 associates with GIPC family endocytic adaptors, we evaluated the requirement for the molecular determinants of their association and PLXND1's vascular role. Zebrafish that endogenously express a Plxnd1 receptor with a predicted impairment in GIPC binding exhibit low penetrance angiogenesis deficits and antiangiogenic drug hypersensitivity. Moreover, gipc mutant fish show angiogenic impairments that are ameliorated by reducing Plxnd1 signaling. Finally, GIPC depletion potentiates SEMA-PLXND1 signaling in cultured endothelial cells. These findings expand the vascular roles of GIPCs beyond those of the Vascular Endothelial Growth Factor (VEGF)-dependent, proangiogenic GIPC1-Neuropilin 1 complex, recasting GIPCs as negative modulators of antiangiogenic PLXND1 signaling and suggest that PLXND1 trafficking shapes vascular development.
Genes / Markers
Figures
Figure Gallery (7 images)
Show all Figures
Expression
No data available
Phenotype
Fish Conditions Stage Phenotype Figure
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt4/skt4; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt4/skt4; y1TgcontrolPrim-15
gipc1skt1/skt1; gipc2skt4/skt4; y1TgcontrolPrim-15
1 - 10 of 42
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fov01b
    		Point Mutation
    s896TgTransgenic Insertion
      skt1
        		Indel
        skt2
          		Insertion
          skt3
            		Indel
            skt4
              		Complex
              skt5
                		Complex
                skt6
                  		Complex
                  skt7TgTransgenic Insertion
                    ubs4TgTransgenic Insertion
                      1 - 10 of 11
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      gipc1CRISPR1-gipc1CRISPR
                      gipc2CRISPR1-gipc2CRISPR
                      gipc2CRISPR2-gipc2CRISPR
                      gipc2CRISPR3-gipc2CRISPR
                      gipc2CRISPR4-gipc2CRISPR
                      gipc3CRISPR1-gipc3CRISPR
                      gipc3CRISPR2-gipc3CRISPR
                      gipc3CRISPR3-gipc3CRISPR
                      plxnd1CRISPR1-plxnd1CRISPR
                      plxnd1MO2-plxnd1MRPHLNO
                      1 - 10 of 10
                      Show
                      Fish
                      Fish
                      gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1Tg
                      gipc1skt1/skt1; gipc2skt3/+; gipc2skt4/+; y1Tg
                      gipc1skt1/skt1; gipc2skt4/skt4; y1Tg
                      gipc1skt1/skt1; gipc2skt4/skt4; y1Tg + MO2-plxnd1
                      gipc1skt1/skt1; y1Tg
                      gipc1skt1/skt1; y1Tg
                      gipc2skt3/+; gipc2skt4/+; y1Tg
                      plxnd1fov01b/fov01b; y1Tg
                      plxnd1fov01b/+; gipc1skt1/skt1; y1Tg
                      plxnd1fov01b/+; plxnd1skt6/+; y1Tg
                      1 - 10 of 13
                      Show
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      mCherryEFGmCherry
                      1 - 3 of 3
                      Show
                      Mapping
                      No data available
                      Your Input Welcome
                      We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
                      Citation
                      Carretero-Ortega, J., Chhangawala, Z., Hunt, S., Narvaez, C., Menéndez-González, J., Gay, C.M., Zygmunt, T., Li, X., Torres-Vázquez, J. (2019) GIPC proteins negatively modulate Plexind1 signaling during vascular development. eLIFE. 8:.