Dataset Information

The homolog of the five SH3-domain protein (HOFI/SH3PXD2B) regulates lamellipodia formation and cell spreading.

ABSTRACT: Motility of normal and transformed cells within and across tissues requires specialized subcellular structures, e.g. membrane ruffles, lamellipodia and podosomes, which are generated by dynamic rearrangements of the actin cytoskeleton. Because the formation of these sub-cellular structures is complex and relatively poorly understood, we evaluated the role of the adapter protein SH3PXD2B [HOFI, fad49, Tks4], which plays a role in the development of the eye, skeleton and adipose tissue. Surprisingly, we find that SH3PXD2B is requisite for the development of EGF-induced membrane ruffles and lamellipodia, as well as for efficient cellular attachment and spreading of HeLa cells. Furthermore, SH3PXD2B is present in a complex with the non-receptor protein tyrosine kinase Src, phosphorylated by Src, which is consistent with SH3PXD2B accumulating in Src-induced podosomes. Furthermore, SH3PXD2B closely follows the subcellular relocalization of cortactin to Src-induced podosomes, EGF-induced membrane ruffles and lamellipodia. Because SH3PXD2B also forms a complex with the C-terminal region of cortactin, we propose that SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via Src and cortactin.

SUBMITTER: Lanyi A

PROVIDER: S-EPMC3160312 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The homolog of the five SH3-domain protein (HOFI/SH3PXD2B) regulates lamellipodia formation and cell spreading.

Lányi Árpád Á Baráth Mónika M Péterfi Zalán Z Bogel Gábor G Orient Anna A Simon Tünde T Petrovszki Eniko E Kis-Tóth Katalin K Sirokmány Gábor G Rajnavölgyi Éva É Terhorst Cox C Buday László L Geiszt Miklós M

PloS one 20110823 8

Motility of normal and transformed cells within and across tissues requires specialized subcellular structures, e.g. membrane ruffles, lamellipodia and podosomes, which are generated by dynamic rearrangements of the actin cytoskeleton. Because the formation of these sub-cellular structures is complex and relatively poorly understood, we evaluated the role of the adapter protein SH3PXD2B [HOFI, fad49, Tks4], which plays a role in the development of the eye, skeleton and adipose tissue. Surprising ...[more]

PMID: 21886807

Similar Datasets

Project description:BackgroundMicroRNAs (miR) are small, posttranscriptional regulators, expressed as part of a longer primary transcript, following which they undergo nuclear and cytoplasmic processing by Drosha and Dicer, respectively, to form the functional mature ~20mer that gets incorporated into the silencing complex. Others and we have shown that mature miR-1 levels decrease with pressure-induced cardiac hypertrophy, however, there is little or no change in the primary transcript encompassing miR-1 stem-loop, suggesting critical regulatory step in microRNA processing. The objective of this study was to investigate the underlying mechanisms regulating miR-1 expression in cardiomyocytes.ResultsHere we report that GTPase-activating protein (SH3 domain) binding protein 1 (G3bp1), an endoribonuclease regulates miR-1 processing in cardiomyocytes. G3bp1 is upregulated during cardiac hypertrophy and restricts miR-1 processing by binding to its consensus sequence in the pre-miR-1-2 stem-loop. In accordance, exogenous G3bp1 is sufficient to reduce miR-1 levels, along with derepression of miR-1 targets; General transcription factor IIB (Gtf2b), cyclin dependent factor 9 (Cdk9) and eukaryotic initiation factor 4E (Eif4e). While Cdk9 and Gtf2b are essential for transcription, Eif4e is required for translation. Thus, downregulation of miR-1 is necessary for increase in these molecules. Similar to miR-1 knockdown, G3bp1 overexpression is not sufficient for development of cardiac hypertrophy. Conversely, knockdown of G3bp1 in hypertrophying cardiomyocytes inhibited downregulation of miR-1 and upregulation of its targets along with restricted hypertrophy, suggesting that G3bp1 is necessary for development of cardiac hypertrophy. These results indicate that G3bp1-mediated inhibition of miR-1 processing with growth stimulation results in decrease in mature miR-1 and, thereby, an increase of its targets, which play fundamental roles in the development of hypertrophy.ConclusionG3bp1 posttranscriptionally regulates miRNA-1 processing in the heart, and G3bp1 mediated downregulation of mature miRNA-1 levels is required for the derepression of its targets and increase in gene expression during cardiac hypertrophy.

Dataset Information

The homolog of the five SH3-domain protein (HOFI/SH3PXD2B) regulates lamellipodia formation and cell spreading.

Publications

The homolog of the five SH3-domain protein (HOFI/SH3PXD2B) regulates lamellipodia formation and cell spreading.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets