scholarly journals Strength Through Unity: The Power of the Mega-Scaffold MACF1

2021 ◽  
Vol 9 ◽  
Author(s):  
Rebecca Cusseddu ◽  
Amélie Robert ◽  
Jean-François Côté
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Tissue Homeostasis ◽  
Actin Microfilaments ◽  
Large Protein ◽  
Cellular Processes ◽  
Support Cell ◽  
Dynamic Events ◽  
Multiple Domains ◽  
Cytoskeletal Dynamic

The tight coordination of diverse cytoskeleton elements is required to support several dynamic cellular processes involved in development and tissue homeostasis. The spectraplakin-family of proteins are composed of multiple domains that provide versatility to connect different components of the cytoskeleton, including the actin microfilaments, microtubules and intermediates filaments. Spectraplakins act as orchestrators of precise cytoskeletal dynamic events. In this review, we focus on the prototypical spectraplakin MACF1, a protein scaffold of more than 700 kDa that coordinates the crosstalk between actin microfilaments and microtubules to support cell-cell connections, cell polarity, vesicular transport, proliferation, and cell migration. We will review over two decades of research aimed at understanding the molecular, physiological and pathological roles of MACF1, with a focus on its roles in developmental and cancer. A deeper understanding of MACF1 is currently limited by technical challenges associated to the study of such a large protein and we discuss ideas to advance the field.

scholarly journals Fine Tuning Cell Migration by a Disintegrin and Metalloproteinases

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
D. Dreymueller ◽  
K. Theodorou ◽  
M. Donners ◽  
A. Ludwig
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Immune Cell ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Tissue Cell ◽  
Cancer Cell Migration ◽  
Physiological Processes ◽  
Cell Tissue ◽  
And Migration

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.

scholarly journals Dynamic behavior of GFP–CLIP-170 reveals fast protein turnover on microtubule plus ends

2008 ◽  
Vol 180 (4) ◽  
pp. 729-737 ◽  
Author(s):  
Katharina A. Dragestein ◽  
Wiggert A. van Cappellen ◽  
Jeffrey van Haren ◽  
George D. Tsibidis ◽  
Anna Akhmanova ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
Cell Polarity ◽  
Protein Turnover ◽  
Structural Changes ◽  
Cellular Processes ◽  
High Affinity ◽  
Division Cell ◽  
Turn Over ◽  
Rate Limiting

Microtubule (MT) plus end–tracking proteins (+TIPs) specifically recognize the ends of growing MTs. +TIPs are involved in diverse cellular processes such as cell division, cell migration, and cell polarity. Although +TIP tracking is important for these processes, the mechanisms underlying plus end specificity of mammalian +TIPs are not completely understood. Cytoplasmic linker protein 170 (CLIP-170), the prototype +TIP, was proposed to bind to MT ends with high affinity, possibly by copolymerization with tubulin, and to dissociate seconds later. However, using fluorescence-based approaches, we show that two +TIPs, CLIP-170 and end-binding protein 3 (EB3), turn over rapidly on MT ends. Diffusion of CLIP-170 and EB3 appears to be rate limiting for their binding to MT plus ends. We also report that the ends of growing MTs contain a surplus of sites to which CLIP-170 binds with relatively low affinity. We propose that the observed loss of fluorescent +TIPs at plus ends does not reflect the behavior of single molecules but is a result of overall structural changes of the MT end.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

Plasticity in designing PROTACs for selective and potent degradation of HDAC6

2019 ◽  
Vol 55 (98) ◽  
pp. 14848-14851 ◽  
Author(s):  
Haiyan Yang ◽  
Wenxing Lv ◽  
Ming He ◽  
Haiteng Deng ◽  
Haitao Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Degradation ◽  
Histone Deacetylase ◽  
Histone Deacetylase 6 ◽  
Cellular Processes

HDAC6 (histone deacetylase 6) catalyses the deacetylation of non-histone substrates, and plays important roles in cell migration, protein degradation and other cellular processes.

scholarly journals Collective cell migration requires suppression of actomyosin at cell–cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6

2010 ◽  
Vol 13 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Cristina Hidalgo-Carcedo ◽  
Steven Hooper ◽  
Shahid I. Chaudhry ◽  
Peter Williamson ◽  
Kevin Harrington ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Cell Cell

scholarly journals Prickle1mutation causes planar cell polarity and directional cell migration defects associated with cardiac outflow tract anomalies and other structural birth defects

Biology Open ◽  
2016 ◽  
Vol 5 (3) ◽  
pp. 323-335 ◽  
Author(s):  
Brian C. Gibbs ◽  
Rama Rao Damerla ◽  
Eszter K. Vladar ◽  
Bishwanath Chatterjee ◽  
Yong Wan ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Birth Defects ◽  
Planar Cell Polarity ◽  
Outflow Tract ◽  
Directional Cell Migration ◽  
Cardiac Outflow

scholarly journals The core planar cell polarity gene, Vangl2 , directs adult corneal epithelial cell alignment and migration

2016 ◽  
Vol 3 (10) ◽  
pp. 160658 ◽  
Author(s):  
Amy S. Findlay ◽  
D. Alessio Panzica ◽  
Petr Walczysko ◽  
Amy B. Holt ◽  
Deborah J. Henderson ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Corneal Epithelium ◽  
Planar Cell Polarity ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
The Core

This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro . Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration.

scholarly journals Truncated Adenomatous Polyposis Coli Mutation Induces Asef-Activated Golgi Fragmentation

2018 ◽  
Vol 38 (17) ◽  
Author(s):  
Sang Bum Kim ◽  
Lu Zhang ◽  
Jimok Yoon ◽  
Jeon Lee ◽  
Jaewon Min ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Adenomatous Polyposis Coli ◽  
Full Length ◽  
Cholesterol Homeostasis ◽  
Dependent Manner ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Golgi Fragmentation ◽  
Cell Cell

ABSTRACT Adenomatous polyposis coli (APC) is a key molecule to maintain cellular homeostasis in colonic epithelium by regulating cell-cell adhesion, cell polarity, and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (Asef). The APC-activated Asef stimulates the small GTPase, which leads to decreased cell-cell adherence and cell polarity, and enhanced cell migration. In colorectal cancers, while truncated APC constitutively activates Asef and promotes cancer initiation and progression, regulation of Asef by full-length APC is still unclear. Here, we report the autoinhibition mechanism of full-length APC. We found that the armadillo repeats in full-length APC interact with the APC residues 1362 to 1540 (APC-2,3 repeats), and this interaction competes off and inhibits Asef. Deletion of APC-2,3 repeats permits Asef interactions leading to downstream signaling events, including the induction of Golgi fragmentation through the activation of the Asef-ROCK-MLC2. Truncated APC also disrupts protein trafficking and cholesterol homeostasis by inhibition of SREBP2 activity in a Golgi fragmentation-dependent manner. Our study thus uncovers the autoinhibition mechanism of full-length APC and a novel gain of function of truncated APC in regulating Golgi structure, as well as cholesterol homeostasis, which provides a potential target for pharmaceutical intervention against colon cancers.

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