Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov;27(4):943-962.
doi: 10.1007/s10456-024-09951-7. Epub 2024 Oct 2.

Angiogenesis is limited by LIC1-mediated lysosomal trafficking

Dymonn Johnson  1 , Sarah Colijn  1 , Jahmiera Richee  1 , Joseph Yano  2   3 , Margaret Burns  2 , Andrew E Davis  2 , Van N Pham  2 , Amra Saric  4   5 , Akansha Jain  4 , Ying Yin  1 , Daniel Castranova  2 , Mariana Melani  2   6   7   8 , Misato Fujita  2   9 , Stephanie Grainger  10 , Juan S Bonifacino  4 , Brant M Weinstein  11 , Amber N Stratman  12
Affiliations

Angiogenesis is limited by LIC1-mediated lysosomal trafficking

Dymonn Johnson et al. Angiogenesis. 2024 Nov.

Abstract

Dynein cytoplasmic 1 light intermediate chain 1 (LIC1, DYNC1LI1) is a core subunit of the dynein motor complex. The LIC1 subunit also interacts with various cargo adaptors to regulate Rab-mediated endosomal recycling and lysosomal degradation. Defects in this gene are predicted to alter dynein motor function, Rab binding capabilities, and cytoplasmic cargo trafficking. Here, we have identified a dync1li1 zebrafish mutant, harboring a premature stop codon at the exon 12/13 splice acceptor site, that displays increased angiogenesis. In vitro, LIC1-deficient human endothelial cells display increases in cell surface levels of the pro-angiogenic receptor VEGFR2, SRC phosphorylation, and Rab11-mediated endosomal recycling. In vivo, endothelial-specific expression of constitutively active Rab11a leads to excessive angiogenesis, similar to the dync1li1 mutants. Increased angiogenesis is also evident in zebrafish harboring mutations in rilpl1/2, the adaptor proteins that promote Rab docking to Lic1 to mediate lysosomal targeting. These findings suggest that LIC1 and the Rab-adaptor proteins RILPL1 and 2 restrict angiogenesis by promoting degradation of VEGFR2-containing recycling endosomes. Disruption of LIC1- and RILPL1/2-mediated lysosomal targeting increases Rab11-mediated recycling endosome activity, promoting excessive SRC signaling and angiogenesis.

Keywords: Angiogenesis; Dynein motor; Endosomes; Lic1; Lysosomes; Rilp1/2; Zebrafish.

PubMed Disclaimer

Conflict of interest statement

Declarations Competing interest The authors declare no competing interests.

Similar articles

  • Regulation of angiogenesis by endocytic trafficking mediated by cytoplasmic dynein 1 light intermediate chain 1.
    Johnson D, Colijn S, Richee J, Yano J, Burns M, Davis AE, Pham VN, Saric A, Jain A, Yin Y, Castranova D, Melani M, Fujita M, Grainger S, Bonifacino JS, Weinstein BM, Stratman AN. Johnson D, et al. bioRxiv [Preprint]. 2024 Apr 1:2024.04.01.587559. doi: 10.1101/2024.04.01.587559. bioRxiv. 2024. PMID: 38903077 Free PMC article. Preprint.
  • CXCR3-CXCL11 Signaling Restricts Angiogenesis and Promotes Pericyte Recruitment.
    Lee J, Goeckel ME, Levitas A, Colijn S, Shin J, Hindes A, Mun G, Burton Z, Chintalapati B, Yin Y, Abello J, Solnica-Krezel L, Stratman AN. Lee J, et al. Arterioscler Thromb Vasc Biol. 2024 Dec;44(12):2577-2595. doi: 10.1161/ATVBAHA.124.321434. Epub 2024 Oct 3. Arterioscler Thromb Vasc Biol. 2024. PMID: 39360413 Free PMC article.
  • Kinesin adapter JLP links PIKfyve to microtubule-based endosome-to-trans-Golgi network traffic of furin.
    Ikonomov OC, Fligger J, Sbrissa D, Dondapati R, Mlak K, Deeb R, Shisheva A. Ikonomov OC, et al. J Biol Chem. 2009 Feb 6;284(6):3750-61. doi: 10.1074/jbc.M806539200. Epub 2008 Dec 4. J Biol Chem. 2009. PMID: 19056739 Free PMC article.
  • Depressing time: Waiting, melancholia, and the psychoanalytic practice of care.
    Salisbury L, Baraitser L. Salisbury L, et al. In: Kirtsoglou E, Simpson B, editors. The Time of Anthropology: Studies of Contemporary Chronopolitics. Abingdon: Routledge; 2020. Chapter 5. In: Kirtsoglou E, Simpson B, editors. The Time of Anthropology: Studies of Contemporary Chronopolitics. Abingdon: Routledge; 2020. Chapter 5. PMID: 36137063 Free Books & Documents. Review.
  • Sexually transmitted infections in Spain: Current status.
    Del Romero J, Moreno Guillén S, Rodríguez-Artalejo FJ, Ruiz-Galiana J, Cantón R, De Lucas Ramos P, García-Botella A, García-Lledó A, Hernández-Sampelayo T, Gómez-Pavón J, González Del Castillo J, Martín-Delgado MC, Martín Sánchez FJ, Martínez-Sellés M, Molero García JM, Gómez Castellá J, Palomo M, García Berrio R, Couso González A, Sotomayor C, Bouza E. Del Romero J, et al. Rev Esp Quimioter. 2023 Oct;36(5):444-465. doi: 10.37201/req/038.2023. Epub 2023 Jun 19. Rev Esp Quimioter. 2023. PMID: 37335757 Free PMC article. Review.
See all similar articles

References

    1. Senger DR, Davis GE (2011) Angiogenesis. Cold Spring Harb Perspect Biol 3(8):a005090. 10.1101/cshperspect.a005090 - DOI - PMC - PubMed
    1. Lamalice L, Le Boeuf F, Huot J (2007) Endothelial cell migration during angiogenesis. Circ Res 100(6):782–794. 10.1161/01.RES.0000259593.07661.1e - DOI - PubMed
    1. Simons M (2012) An inside view: VEGF receptor trafficking and signaling. Physiology 27(4):213–222. 10.1152/physiol.00016.2012 - DOI - PMC - PubMed
    1. Watanabe C, Matsushita J, Azami T et al. (2019) Generating Vegfr3 reporter transgenic mouse expressing membrane-tagged venus for visualization of VEGFR3 expression in vascular and lymphatic endothelial cells. PLoS ONE 14(1):e0210060. 10.1371/journal.pone.0210060 - DOI - PMC - PubMed
    1. Jouette J, Guichet A, Claret SB (2019) Dynein-mediated transport and membrane trafficking control PAR3 polarised distribution. Elife. 10.7554/eLife.40212 - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources