scholarly journals Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis

2016 ◽  
Author(s):  
Amandine Pitaval ◽  
Fabrice Senger ◽  
Gaëlle Letort ◽  
Xavier Gidrol ◽  
Laurent Guyon ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilia ◽  
Mechanical Forces ◽  
Apical Surface ◽  
Microtubule Network ◽  
Microtubule Stabilization ◽  
Cytoskeletal Remodeling ◽  
Cell Architecture ◽  
Cytoskeleton Remodeling ◽  
Insight Into

AbstractPrimary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to the apical surface. Yet surprisingly little is known about this initiating step. To gain insight into the mechanisms driving centrosome migration, we exploited the reproducibility of cell architecture on adhesive micropatterns to investigate the cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with the transient formation of an array of cold-stable microtubules, and actin cytoskeleton asymmetric contraction participated in concert to destabilize basal centrosome position and drive apical centrosome migration. The distal appendage protein Cep164 appeared to be a key actor involved in the cytoskeleton remodeling and centrosome migration, whereas IFT88's role seemed to be restricted to axoneme elongation. Together our data elucidate the hitherto unexplored mechanism of centrosome migration and show that it is driven by the increase and clustering of mechanical forces to push the centrosome toward the cell apical pole.

scholarly journals Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis

2017 ◽  
Vol 216 (11) ◽  
pp. 3713-3728 ◽  
Author(s):  
Amandine Pitaval ◽  
Fabrice Senger ◽  
Gaëlle Letort ◽  
Xavier Gidrol ◽  
Laurent Guyon ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Intraflagellar Transport ◽  
Mechanical Forces ◽  
Apical Surface ◽  
Microtubule Network ◽  
Microtubule Stabilization ◽  
Cytoskeletal Remodeling ◽  
Cell Architecture ◽  
Cytoskeleton Remodeling ◽  
Insight Into

Primary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to the apical surface, yet surprisingly little is known about this initiating step. To gain insight into the mechanisms driving centrosome migration, we exploited the reproducibility of cell architecture on adhesive micropatterns to investigate the cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with the transient formation of an array of cold-stable microtubules, and actin cytoskeleton asymmetrical contraction participate in concert to drive apical centrosome migration. The distal appendage protein Cep164 appears to be a key actor involved in the cytoskeleton remodeling and centrosome migration, whereas intraflagellar transport 88’s role seems to be restricted to axoneme elongation. Together, our data elucidate the hitherto unexplored mechanism of centrosome migration and show that it is driven by the increase and clustering of mechanical forces to push the centrosome toward the cell apical pole.

Numerical Simulation of Blood Flow in Patient-Specific Stenotic Carotid Bifurcation Geometries

2009 ◽  
Author(s):  
Megan Cummins ◽  
Jenn S. Rossmann
Keyword(s):  
Vortex Shedding ◽  
Carotid Bifurcation ◽  
Secondary Flows ◽  
Patient Specific ◽  
Mechanical Forces ◽  
Plaque Vulnerability ◽  
Governing Equations ◽  
Unstable Plaque ◽  
Recirculation Zones ◽  
Insight Into

The hemodynamics and fluid mechanical forces in blood vessels have long been implicated in the deposition and growth of atherosclerotic plaque. Detailed information about the hemodynamics in vessels affected by significant plaque deposits can provide insight into the mechanisms and likelihood of plaque weakening and rupture. In the current study, the governing equations are solved in their finite volume formulation in several patient-specific geometries. Recirculation zones, vortex shedding, and secondary flows are captured. The forces on vessel walls are shown to correlate with unstable plaque deposits. The results of these simulations suggest morphological features that may usefully supplement percent stenosis as a predictor of plaque vulnerability.

Intracellular traffic of the ecto-nucleotide pyrophosphatase/phosphodiesterase NPP3 to the apical plasma membrane of MDCK and Caco-2 cells: apical targeting occurs in the absence of N-glycosylation

2000 ◽  
Vol 113 (23) ◽  
pp. 4193-4202 ◽  
Author(s):  
N.R. Meerson ◽  
V. Bello ◽  
J.L. Delaunay ◽  
T.A. Slimane ◽  
D. Delautier ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mdck Cells ◽  
Transmembrane Proteins ◽  
Cell Types ◽  
Apical Plasma Membrane ◽  
Apical Surface ◽  
Intracellular Traffic ◽  
Transmembrane Glycoprotein ◽  
Direct Demonstration ◽  
Targeting Signal

Glycosylation was considered the major signal candidate for apical targeting of transmembrane proteins in polarized epithelial cells. However, direct demonstration of the role of glycosylation has proved difficult because non-glycosylated apical transmembrane proteins usually do not reach the cell surface. Here we were able to follow the targeting of the apical transmembrane glycoprotein NPP3 both when glycosylated and non-glycosylated. Transfected in polarized MDCK and Caco-2 cells, NPP3 was exclusively expressed at the apical membrane. The transport kinetics of the protein to the cell surface were studied after metabolic (35)S-labeling and surface immunoprecipitation. The newly synthesized protein was mainly targeted directly to the apical surface in MDCK cells, whereas 50% transited through the basolateral surface in Caco-2 cells. In both cell types, the basolaterally targeted pool was effectively transcytosed to the apical surface. In the presence of tunicamycin, NPP3 was not N-glycosylated. The non-glycosylated protein was partially retained intracellularly but the fraction that reached the cell surface was nevertheless predominantly targeted apically. However, transcytosis of the non-glycosylated protein was partially impaired in MDCK cells. These results provide direct evidence that glycosylation cannot be considered an apical targeting signal for NPP3, although glycosylation is necessary for correct trafficking of the protein to the cell surface.

Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

Adhesion of uric acid crystals to the surface of renal epithelial cells

2000 ◽  
Vol 278 (6) ◽  
pp. F989-F998 ◽  
Author(s):  
Rima M. Koka ◽  
Erick Huang ◽  
John C. Lieske
Keyword(s):  
Uric Acid ◽  
Epithelial Cells ◽  
Cell Surface ◽  
Hydrophobic Interactions ◽  
Calcium Phosphates ◽  
Apical Cell ◽  
Apical Surface ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Renal Tubular Cells

Adhesion of microcrystals that nucleate in tubular fluid to the apical surface of renal tubular cells could be a critical step in the formation of kidney stones, 12% of which contain uric acid (UA) either alone or admixed with calcium oxalates or calcium phosphates. UA crystals bind rapidly to monolayer cultures of monkey kidney epithelial cells (BSC-1 line), used to model the surface of the nephron, in a concentration-dependent manner. The urinary glycoproteins osteopontin, nephrocalcin, and Tamm-Horsfall glycoprotein had no effect on binding of UA crystals to the cell surface, whereas other polyanions including specific glycosaminoglycans blocked UA crystal adhesion. Specific polycations also inhibited adhesion of UA crystals and appeared to exert their inhibitory effect by coating cells. However, removal of anionic cell surface molecules with neuraminidase, heparitinase I, or chondroitinase ABC each increased UA crystal binding, and sialic acid-binding lectins had no effect. These observations suggest that hydrogen bonding and hydrophobic interactions play a major role in adhesion of electrostatically neutral UA crystals to renal cells, unlike the interaction of calcium-containing crystals with negatively charged molecules on the apical cell surface via ionic forces. After adhesion to the plasma membrane, subsequent cellular events could contribute to UA crystal retention in the kidney and the development of UA or mixed calcium and UA calculi.

scholarly journals A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes

2021 ◽  
Vol 8 ◽  
Author(s):  
Leticia Labat-de-Hoz ◽  
Armando Rubio-Ramos ◽  
Javier Casares-Arias ◽  
Miguel Bernabé-Rubio ◽  
Isabel Correas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Control Cell ◽  
Future Research ◽  
Alternative Route ◽  
Ciliary Membrane ◽  
Cilium Formation ◽  
Membrane Compartmentalization

Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

scholarly journals Tannerella forsythiastrains display different cell-surface nonulosonic acids: biosynthetic pathway characterization and first insight into biological implications

Glycobiology ◽  
2016 ◽  
Author(s):  
Valentin Friedrich ◽  
Bettina Janesch ◽  
Markus Windwarder ◽  
Daniel Maresch ◽  
Matthias L. Braun ◽  
...  
Keyword(s):  
Cell Surface ◽  
Biosynthetic Pathway ◽  
Insight Into

scholarly journals Primary cilium and glioblastoma

2018 ◽  
Vol 10 ◽  
pp. 175883591880116 ◽  
Author(s):  
María Álvarez-Satta ◽  
Ander Matheu
Keyword(s):  
Cancer Progression ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Apical Surface ◽  
New Approach ◽  
Primary Brain Tumour ◽  
Tumorigenesis And Progression ◽  
Signalling Transduction ◽  
Abnormal Cilia

Glioblastoma (GBM) represents the most common, malignant and lethal primary brain tumour in adults. The primary cilium is a highly conserved and dynamic organelle that protrudes from the apical surface of virtually every type of mammalian cell. There is increasing evidence that abnormal cilia are involved in cancer progression, since primary cilia regulate cell cycle and signalling transduction. In this review, we summarize the role of primary cilium specifically with regard to GBM, where there is evidence postulating it as a critical mediator of GBM tumorigenesis and progression. This opens the way to the application of cilia-targeted therapies (‘ciliotherapy’) as a new approach in the fight against this devastating tumour.

Epithelial sorting of a glycosylphosphatidylinositol-anchored bacterial protein expressed in polarized renal MDCK and intestinal Caco-2 cells

1995 ◽  
Vol 108 (1) ◽  
pp. 369-377 ◽  
Author(s):  
K.L. Soole ◽  
M.A. Jepson ◽  
G.P. Hazlewood ◽  
H.J. Gilbert ◽  
B.H. Hirst
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Intestinal Epithelial Cells ◽  
Mdck Cells ◽  
Basolateral Membrane ◽  
Apical Cell ◽  
Apical Surface ◽  
Intestinal Epithelial ◽  
Gpi Anchor ◽  
Sorting Signal

To evaluate whether a glycosylphosphatidylinositol (GPI) anchor can function as a protein sorting signal in polarized intestinal epithelial cells, the GPI-attachment sequence from Thy-1 was fused to bacterial endoglucanase E' (EGE') from Clostridium thermocellum and polarity of secretion of the chimeric EGE'-GPI protein was evaluated. The chimeric EGE'-GPI protein was shown to be associated with a GPI anchor by TX-114 phase-partitioning and susceptibility to phosphoinositol-specific phospholipase C. In polarized MDCK cells, EGE' was localized almost exclusively to the apical cell surface, while in polarized intestinal Caco-2 cells, although 80% of the extracellular form of the enzyme was routed through the apical membrane over a 24 hour period, EGE' was also detected at the basolateral membrane. Rates of delivery of EGE'-GPI to the two membrane domains in Caco-2 cells, as determined with a biotinylation protocol, revealed apical delivery was approximately 2.5 times that of basolateral. EGE' delivered to the basolateral cell surface was transcytosed to the apical surface. These data indicate that a GPI anchor does represent a dominant apical sorting signal in intestinal epithelial cells. However, the mis-sorting of a proportion of EGE'GPI to the basolateral surface of Caco-2 cells provides an explanation for additional sorting signals in the ectodomain of some endogenous GPI-anchored proteins.

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