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

被引：16

作者：

Joshi, Divyesh ^{[1
]}

Inamdar, Maneesha S. ^{[1
,2
]}

机构：

[1] Jawaharlal Nehru Ctr Adv Sci Res, Mol Biol & Genet Unit, Bangalore 560064, Karnataka, India

[2] Inst Stem Cell Biol & Regenerat Med, Bangalore 560065, Karnataka, India

来源：

MOLECULAR BIOLOGY OF THE CELL | 2019年 / 30卷 / 12期

基金：

英国惠康基金;

关键词：

VIMENTIN; ADHESION; PROTEIN; CYTOSKELETON;

D O I：

10.1091/mbc.E18-08-0484

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1437 / 1450

页数：14

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