PUBLICATION
Inner nuclear membrane protein TMEM201 maintains endothelial cell migration and angiogenesis by interacting with the LINC complex
- Authors
- Zhang, Y., Kong, Y., Guo, H., Liu, Y., Zang, Y., Li, J.
- ID
- ZDB-PUB-220323-17
- Date
- 2022
- Source
- Journal of molecular cell biology 14(3): (Journal)
- Registered Authors
- Keywords
- LINC complex, angiogenesis, endothelial cell, inner nuclear membrane, migration, transmembrane protein 201
- MeSH Terms
-
- Animals
- Cell Movement
- Human Umbilical Vein Endothelial Cells*/cytology
- Human Umbilical Vein Endothelial Cells*/metabolism
- Humans
- Membrane Proteins*/genetics
- Mice
- Neovascularization, Physiologic*
- Nuclear Envelope*/metabolism
- Nuclear Proteins*/genetics
- Zebrafish/metabolism
- PubMed
- 35311970 Full text @ J. Mol. Cell Biol.
Citation
Zhang, Y., Kong, Y., Guo, H., Liu, Y., Zang, Y., Li, J. (2022) Inner nuclear membrane protein TMEM201 maintains endothelial cell migration and angiogenesis by interacting with the LINC complex. Journal of molecular cell biology. 14(3).
Abstract
The nuclear envelope comprises the outer nuclear membrane (ONM), inner nuclear membrane (INM), and nucleopore. Although ∼60 INM proteins have been identified, only a few of them have been well characterized, revealing their crucial roles. Our group focused on the INM protein transmembrane protein 201 (TMEM201), whose role in cellular function remains to be defined. In this study, we investigated the role of TMEM201 in endothelial cell migration and angiogenesis. Depletion of TMEM201 expression by short hairpin RNA-mediated interference impeded human umbilical vein endothelial cell (HUVEC) angiogenic behavior in tube formation and fibrin gel bead sprouting assays. Meanwhile, TMEM201-deficient HUVEC exhibited impaired migration ability. We next explored the underlying mechanism and found that the N-terminal of TMEM201 interacted with the linker of nucleoskeleton and cytoskeleton (LINC) complex and was required for regulating endothelial cell migration and angiogenesis. The above in vitro findings were further confirmed by using in vivo models. In Tmem201-knockout mice, retinal vessel development was arrested and aortic ring sprouting was defective. In addition, loss of tmem201 impaired zebrafish intersegmental vessel development. In summary, TMEM201 was shown to regulate endothelial cell migration and control the process of angiogenesis. This study is the first to reveal the role of INM proteins in the vascular system and angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping