MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway

Bravo‐Cordero, Jose Javier; Marrero-Diaz, Raquel; Megı́as, Diego; Genı́s, Laura; García-Grande, Aránzazu; García, María Ángel; Arroyo, Alicia G.; Montoya, Marı́a C.

doi:10.1038/sj.emboj.7601606

Cited by 226 publications

(225 citation statements)

References 52 publications

Supporting

Mentioning

213

Contrasting

Unclassified

Order By: Relevance

“…56 Furthermore, Rab8 drives cellular invasion by trafficking the matrix metalloproteinase MT1-MMP to the plasma membrane. 57 Most recently, Rab8 activation has been shown to induce Rac1 activity, causing cortical actin formation, focal adhesion disassembly, and stress fiber disassembly. 58 This effect was dependent on Calpain, MT1-MMP, and Rho GTPases.…”

Section: Molecular Control Of Calcium Influxes Upon Induction Of Epitmentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

View full text Add to dashboard Cite

Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelialmesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases.

show abstract

Section: Molecular Control Of Calcium Influxes Upon Induction Of Epitmentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

View full text Add to dashboard Cite

show abstract

“…26 In particular, RAB8A is known as one of the main regulators of membrane fusion and exocytosis. 13,27 To determine whether RAB8A regulates IDE secretion from astrocytes, we treated the Rab8a and Rab5 (as control) siRNA-transfected cells with Ab ( Fig. 5A and S5A).…”

Section: Ab-induced Ide Secretion Is Mediated By Rab8a Activitymentioning

confidence: 99%

Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease

et al. 2016

View full text Add to dashboard Cite

The secretion of proteins that lack a signal sequence to the extracellular milieu is regulated by their transition through the unconventional secretory pathway. IDE (insulin-degrading enzyme) is one of the major proteases of amyloid beta peptide (Ab), a presumed causative molecule in Alzheimer disease (AD) pathogenesis. IDE acts in the extracellular space despite having no signal sequence, but the underlying mechanism of IDE secretion extracellularly is still unknown. In this study, we found that IDE levels were reduced in the cerebrospinal fluid (CSF) of patients with AD and in pathology-bearing AD-model mice. Since astrocytes are the main cell types for IDE secretion, astrocytes were treated with Ab. Ab increased the IDE levels in a time-and concentration-dependent manner. Moreover, IDE secretion was associated with an autophagy-based unconventional secretory pathway, and depended on the activity of RAB8A and GORASP (Golgi reassembly stacking protein). Finally, mice with global haploinsufficiency of an essential autophagy gene, showed decreased IDE levels in the CSF in response to an intracerebroventricular (i.c.v.) injection of Ab. These results indicate that IDE is secreted from astrocytes through an autophagy-based unconventional secretory pathway in AD conditions, and that the regulation of autophagy is a potential therapeutic target in addressing Ab pathology.

show abstract

“…It has been shown previously that MT1-MMP is recycled back to the cell surface in Rab4-positive recycling endosomes in HT1080 cells, in a setting where MT1-MMP is not involved in extracellular matrix degradation (30). However, when MDA-MB-231 cells were cultured in a three-dimensional type I collagen matrix, MT1-MMP was recruited from an intracellular storage compartment, different from the recycling endosomes, in Rab8-positive exocytic vesicles (64). Accordingly, we observed a difference in cellular invasion and migration in cells cultured in two dimensions versus three dimensions, with a reduction of cell invasion in the MT1-K581R expressing cells in two dimensions and no apparent change in spheroid outgrowth compared with MT1-WT expressing cells (supplemental Fig.…”

Section: Discussionmentioning

confidence: 95%

Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Ubiquitination at Lys581 Increases Cellular Invasion through Type I Collagen

Eisenach

Sampaio

Murphy

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: MT1-MMP is a membrane-anchored matrix metalloproteinase involved in pericellular proteolysis and invasion. Results: MT1-MMP is monoubiquitinated intracellularly at Lys 581 , modulating intracellular trafficking and cellular invasion. Conclusion: Regulation of the activity of MT1-MMP by monoubiquitination emphasizes the importance of its intracellular domain during MT1-MMP-driven cellular invasion. Significance: Given the key role MT1-MMP plays in pathological conditions, a better understanding of the regulation of MT1-MMP is essential for therapeutic intervention.

show abstract

MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway

Cited by 226 publications

References 52 publications

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

Insulin-degrading enzyme secretion from astrocytes is mediated by an autophagy-based unconventional secretory pathway in Alzheimer disease

Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Ubiquitination at Lys581 Increases Cellular Invasion through Type I Collagen

Contact Info

Product

Resources

About