RECK isoforms differentially regulate fibroblast migration by modulating tubulin post-translational modifications.
Biochem Biophys Res Commun
; 510(2): 211-218, 2019 03 05.
Article
en En
| MEDLINE
| ID: mdl-30704758
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tubulina (Proteína)
/
Procesamiento Proteico-Postraduccional
/
Proteínas Ligadas a GPI
/
Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos