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PMID:22300583

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Citation

Jain, M, Bhat, GP, Vijayraghavan, K and Inamdar, MS (2012) Rudhira/BCAS3 is a cytoskeletal protein that controls Cdc42 activation and directional cell migration during angiogenesis. Exp. Cell Res. 318:753-67

Abstract

Cell migration is a common cellular process in angiogenesis and tumor metastasis. Rudhira/BCAS3 (Breast Cancer Amplified Sequence 3) is a conserved protein expressed in the embryonic vasculature and malignant tumors. Here, we show for the first time that Rudhira plays an active role in directional cell migration. Rudhira depletion in endothelial cells inhibits Matrigel-induced tube formation and retards healing of wounded cell monolayers. We demonstrate that during wound healing, Rudhira rapidly re-localizes and promotes Cdc42 activation and recruitment to the leading edge of migrating cells. Rudhira deficient cells show impaired downstream signaling of Cdc42 leading to dramatic changes in actin organization and classic cell polarity defects such as loss of microtubule organizing center (MTOC) and Golgi re-orientation. Biochemical assays and co-localization studies show that Rudhira interacts with microtubules as well as intermediate filaments. Thus, Rudhira could control directional cell migration and angiogenesis by facilitating crosstalk between cytoskeletal elements.

Links

PubMed Online version:10.1016/j.yexcr.2012.01.016

Keywords

Animals; Cell Movement; Cytoskeletal Proteins/metabolism; Cytoskeleton/metabolism; Endothelial Cells/metabolism; HEK293 Cells; Humans; Mice; NIH 3T3 Cells; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Neovascularization, Pathologic/metabolism; Transfection; cdc42 GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:VIME

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H6U6

F

Seeded From UniProt

complete

MOUSE:BCAS3

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0034260: negative regulation of GTPase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

located_in

GO:0045111: intermediate filament cytoskeleton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0007030: Golgi organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0031023: microtubule organizing center organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0010595: positive regulation of endothelial cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

located_in

GO:0031252: cell leading edge

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BCAS3

located_in

GO:0005881: cytoplasmic microtubule

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0051895: negative regulation of focal adhesion assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0051491: positive regulation of filopodium assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:2000251: positive regulation of actin cytoskeleton reorganization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0043547: positive regulation of GTPase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0090630: activation of GTPase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0090316: positive regulation of intracellular protein transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:2000114: regulation of establishment of cell polarity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BCAS3

involved_in

GO:0035148: tube formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BCAS3

enables

GO:0048487: beta-tubulin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:BCAS3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P08670

F

Seeded From UniProt

complete

See also

References

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