Research output: Contribution to journal › Article › peer-review
Nisha Bte Mohd Rafiq, Zi Zhao Lieu, Tingting Jiang, Cheng Han Yu, Paul Matsudaira, Gareth E. Jones, Alexander D. Bershadsky
Original language | English |
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Pages (from-to) | 181-197 |
Number of pages | 17 |
Journal | The Journal of cell biology |
Volume | 216 |
Issue number | 1 |
Early online date | 22 Dec 2016 |
DOIs | |
Accepted/In press | 28 Nov 2016 |
E-pub ahead of print | 22 Dec 2016 |
Published | 31 Jan 2017 |
Additional links |
Podosome assembly is controlled by the GTPase_RAFIQ_Published22December2016_GOLD VoR
Podosome_assembly_is_controlled_by_the_GTPase_RAFIQ_Published22December2016_GOLD_VoR.pdf, 2.86 MB, application/pdf
Uploaded date:04 Jan 2017
Version:Final published version
Licence:CC BY-NC-SA
Podosomes represent a class of integrin-mediated cell-matrix adhesions formed by migrating and matrix-degrading cells. We demonstrate that in macrophage-like THP1 cells and fibroblasts stimulated to produce podosomes, down-regulation of the G-protein ARF1 or the ARF1 guanine nucleotide exchange factor, ARNO, by small, interfering RNA or pharmacological inhibitors led to striking podosome elimination. Concomitantly, treatments inducing podosome formation increased the level of guanosine triphosphate (GTP)-bound ARF1. ARNO was found to colocalize with the adhesive rings of podosomes, whereas ARF1 was localized to vesicular structures transiently contacting podosome rings. Inhibition of ARF1 led to an increase in RhoA-GTP levels and triggered assembly of myosin-IIA filaments in THP1 cells, whereas the suppression of myosin-IIA rescued podosome formation regardless of ARF1 inhibition. Finally, expression of constitutively active ARF1 in fibroblasts induced formation of putative podosome precursors: Actin-rich puncta coinciding with matrix degradation sites and containing proteins of the podosome core but not of the adhesive ring. Thus, ARNO-ARF1 regulates formation of podosomes by inhibition of RhoA/myosin-II and promotion of actin core assembly.
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