Rudhira/BCAS3 couples microtubules and intermediate filaments to promote cell migration for angiogenic remodeling

Blood vessel formation requires endothelial cell (EC) migration that depends on dynamic remodeling of the cytoskeleton. Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein essential for EC migration and sprouting angiogenesis during mouse development and is implicated in...

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Bibliographic Details
Published in:Molecular biology of the cell 2019-06, Vol.30 (12), p.1437-1450
Main Authors: Joshi, Divyesh, Inamdar, Maneesha S
Format: Article
Language:English
Subjects:
Animals
Cell Movement
Focal Adhesions - metabolism
HEK293 Cells
HeLa Cells
Humans
Intermediate Filaments - metabolism
Mice
Microtubules - metabolism
Neoplasm Proteins - chemistry
Neoplasm Proteins - metabolism
Neovascularization, Physiologic
Protein Domains
Vimentin - metabolism
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Summary:Blood vessel formation requires endothelial cell (EC) migration that depends on dynamic remodeling of the cytoskeleton. Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein essential for EC migration and sprouting angiogenesis during mouse development and is implicated in metastatic disease. Here, we report that Rudhira mediates cytoskeleton organization and dynamics during EC migration. Rudhira binds to both microtubules (MTs) and vimentin intermediate filaments (IFs) and stabilizes MTs. Rudhira depletion impairs cytoskeletal cross-talk, MT stability, and hence focal adhesion disassembly. The BCAS3 domain of Rudhira is necessary and sufficient for MT-IF cross-linking and cell migration. Pharmacologically restoring MT stability rescues gross cytoskeleton organization and angiogenic sprouting in Rudhira-depleted cells. Our study identifies the novel and essential role of Rudhira in cytoskeletal cross-talk and assigns function to the conserved BCAS3 domain. Targeting Rudhira could allow tissue-restricted cytoskeleton modulation to control cell migration and angiogenesis in development and disease.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e18-08-0484