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Biochem Biophys Res Commun. 2019 Mar 5;510(2):211-218. doi: 10.1016/j.bbrc.2019.01.063. Epub 2019 Jan 28.

RECK isoforms differentially regulate fibroblast migration by modulating tubulin post-translational modifications.

Author information

1
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
2
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
3
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, 90095, USA; Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, Los Angeles, CA, 90095, USA. Electronic address: hcoller@ucla.edu.

Abstract

Cell migration is essential for proper development and the defense against pathogens. Our previous work detailed a pathway of REversion-inducing-Cysteine-rich protein with Kazal motifs (RECK) isoform-mediated invasion in which a shorter RECK protein competes with MMP9 for interaction with the canonical RECK protein on the cell surface. Here we demonstrate that the mechanism through which RECK isoforms affect cell migration is mediated through changes in the levels of post-translational modifications (PTM) of α-tubulin. We show that both the canonical and short RECK isoforms modulate levels of tubulin acetylation and detyrosination. We demonstrate that these changes are sufficient to modulate the rate of fibroblast migration. If these tubulin PTMs are not altered, the effects of the canonical RECK isoform on cell migration are reversed. In defining the molecular pathway linking RECK and tubulin PTMs, we found that MMP9 and integrin activity both act as upstream regulators of tubulin acetylation and detyrosination. Overall, we propose a mechanism in which RECK isoforms on the cell surface have opposing effects on cell migration through MMP9-modulated changes to integrin-extracellular matrix (ECM) interactions that, in turn, affect microtubule PTMs.

KEYWORDS:

Fibroblast migration; Integrin; MMP9; RECK isoforms; Tubulin PTM

PMID:
30704758
DOI:
10.1016/j.bbrc.2019.01.063

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