scholarly journals VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and migration

Development ◽  
2012 ◽  
Vol 139 (14) ◽  
pp. e1-e1
Author(s):  
B. B. Williams ◽  
V. A. Cantrell ◽  
N. A. Mundell ◽  
A. C. Bennett ◽  
R. E. Quick ◽  
...  
2012 ◽  
Vol 125 (9) ◽  
pp. 2141-2147 ◽  
Author(s):  
B. B. Williams ◽  
V. A. Cantrell ◽  
N. A. Mundell ◽  
A. C. Bennett ◽  
R. E. Quick ◽  
...  

2018 ◽  
Author(s):  
Ye Dee Tay ◽  
Marcin Leda ◽  
Christos Spanos ◽  
Juri Rappsilber ◽  
Andrew B. Goryachev ◽  
...  

ABSTRACTNDR/LATS kinases regulate multiple aspects of cell polarity and morphogenesis from yeast to mammals, but few of their substrates are known. Fission yeast NDR/LATS kinase Orb6 has been proposed to control cell polarity via spatial regulation of Gef1, a guanine nucleotide exchange factor for the small GTPase Cdc42. Here we show that Orb6 plays a critical role as a positive regulator of exocytosis, independent of Gef1. Through Orb6 inhibition in vivo and quantitative global phosphoproteomics, we identify several proteins involved in membrane trafficking as Orb6 targets, and we confirm Sec3 and Sec5, conserved components of the exocyst complex, as substrates of Orb6 both in vivo and in vitro. Our results suggest that Orb6 kinase activity is crucial for exocyst localization to actively-growing cell tips and for exocyst activity during septum dissolution after cytokinesis. We further show that Orb6 phosphorylation of Sec3 serine-201 contributes to exocyst function in parallel with exocyst protein Exo70. We propose that Orb6 contributes to polarized growth by regulating membrane trafficking at multiple levels.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Julie Jouette ◽  
Antoine Guichet ◽  
Sandra B Claret

The scaffold protein PAR3 and the kinase PAR1 are essential proteins that control cell polarity. Their precise opposite localisations define plasma membrane domains with specific functions. PAR3 and PAR1 are mutually inhibited by direct or indirect phosphorylations, but their fates once phosphorylated are poorly known. Through precise spatiotemporal quantification of PAR3 localisation in the Drosophila oocyte, we identify several mechanisms responsible for its anterior cortex accumulation and its posterior exclusion. We show that PAR3 posterior plasma membrane exclusion depends on PAR1 and an endocytic mechanism relying on RAB5 and PI(4,5)P2. In a second phase, microtubules and the dynein motor, in connection with vesicular trafficking involving RAB11 and IKK-related kinase, IKKε, are required for PAR3 transport towards the anterior cortex. Altogether, our results point to a connection between membrane trafficking and dynein-mediated transport to sustain PAR3 asymmetry.


2018 ◽  
Vol 115 (34) ◽  
pp. 8581-8586 ◽  
Author(s):  
Pengbo Wang ◽  
Marcel Dreger ◽  
Elena Madrazo ◽  
Craig J. Williams ◽  
Rafael Samaniego ◽  
...  

Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5. Similarly, depletion of RbBP5 (another H3K4 methyltransferase subunit) promotes similar defects. We reveal that a 3D environment increases the H3K4 methylation dependent on WDR5 and results in a globally less compacted chromatin conformation. Further, using atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments, we detect changes in nuclear mechanics that accompany the epigenetic changes induced in 3D conditions. Indeed, nuclei from cells in 3D environments were softer, and thereby more deformable, compared with cells in suspension or cultured in 2D conditions, again dependent on WDR5. Dissecting the underlying mechanism, we determined that actomyosin contractility, through the phosphorylation of myosin by MLCK (myosin light chain kinase), controls the interaction of WDR5 with other components of the methyltransferase complex, which in turn up-regulates H3K4 methylation activation in 3D conditions. Taken together, our findings reveal a nongenomic function for WDR5 in regulating H3K4 methylation induced by 3D environments, physical properties of the nucleus, cell polarity, and cell migratory capacity.


2016 ◽  
Vol 8 (7) ◽  
pp. 741-750 ◽  
Author(s):  
Philipp J. Albert ◽  
Ulrich S. Schwarz

Adhesive micropatterns have become a standard tool to control cell shape and function in cell culture.


2015 ◽  
Vol 14 (12) ◽  
pp. 3132-3141 ◽  
Author(s):  
Janel R. Beckley ◽  
Jun-Song Chen ◽  
Yanling Yang ◽  
Junmin Peng ◽  
Kathleen L. Gould

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
D. Dreymueller ◽  
K. Theodorou ◽  
M. Donners ◽  
A. Ludwig

Cell migration is an instrumental process involved in organ development, tissue homeostasis, and various physiological processes and also in numerous pathologies. Both basic cell migration and migration towards chemotactic stimulus consist of changes in cell polarity and cytoskeletal rearrangement, cell detachment from, invasion through, and reattachment to their neighboring cells, and numerous interactions with the extracellular matrix. The different steps of immune cell, tissue cell, or cancer cell migration are tightly coordinated in time and place by growth factors, cytokines/chemokines, adhesion molecules, and receptors for these ligands. This review describes how a disintegrin and metalloproteinases interfere with several steps of cell migration, either by proteolytic cleavage of such molecules or by functions independent of proteolytic activity.


Science ◽  
2010 ◽  
Vol 329 (5997) ◽  
pp. 1337-1340 ◽  
Author(s):  
Su Kyoung Kim ◽  
Asako Shindo ◽  
Tae Joo Park ◽  
Edwin C. Oh ◽  
Srimoyee Ghosh ◽  
...  

The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease.


2011 ◽  
Vol 13 (10) ◽  
pp. B395-B404 ◽  
Author(s):  
Mar Diez ◽  
Vera A. Schulte ◽  
Filippo Stefanoni ◽  
Carlo F. Natale ◽  
Francesco Mollica ◽  
...  

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