Peptide aptamers as new tools to modulate clathrin-mediated internalisation--inhibition of MT1-MMP internalisation.

BMC Cell Biology
Rochana D WickramasingheChristian Roghi

Abstract

Peptide aptamers are combinatorial protein reagents that bind to targets with a high specificity and a strong affinity thus providing a molecular tool kit for modulating the function of their targets in vivo. Here we report the isolation of a peptide aptamer named swiggle that interacts with the very short (21 amino acid long) intracellular domain of membrane type 1-metalloproteinase (MT1-MMP), a key cell surface protease involved in numerous and crucial physiological and pathological cellular events. Expression of swiggle in mammalian cells was found to increase the cell surface expression of MT1-MMP by impairing its internalisation. Swiggle interacts with the LLY573 internalisation motif of MT1-MMP intracellular domain, thus disrupting the interaction with the mu2 subunit of the AP-2 internalisation complex required for endocytosis of the protease. Interestingly, swiggle-mediated inhibition of MT1-MMP clathrin-mediated internalisation was also found to promote MT1-MMP-mediated cell migration. Taken together, our results provide further evidence that peptide aptamers can be used to dissect molecular events mediated by individual protein domains, in contrast to the pleiotropic effects of RNA interference techniques.

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Citations

Jul 5, 2011·The Journal of Biological Chemistry·François BéliveauRichard Leduc
May 28, 2011·Protein Engineering, Design & Selection : PEDS·Lukas Kurt Josef StadlerPaul Ko Ferrigno
Jan 31, 2014·Molecular Biology of the Cell·Karolina LeśniewskaHiroyuki Ohkura
Oct 24, 2012·The Journal of Cell Biology·Xinzi YuLaura M Machesky
May 4, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pablo F BarcelonaGustavo A Chiabrando

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Methods Mentioned

BETA
phage-display
two-hybrid
fluorescence microscopy
immunoprecipitation
co-immunoprecipitation
two hybrid
dissection
PCR
FCS
Assay

Software Mentioned

Metamorph
Zeiss AIM

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