scholarly journals A Presenilin-2–ARF4 trafficking axis modulates Notch signaling during epidermal differentiation

2016 ◽  
Vol 214 (1) ◽  
pp. 89-101 ◽  
Author(s):  
Ellen J. Ezratty ◽  
H. Amalia Pasolli ◽  
Elaine Fuchs
Keyword(s):  
Notch Signaling ◽  
Basal Body ◽  
Primary Cilia ◽  
Small Gtpase ◽  
Epidermal Differentiation ◽  
Basal Bodies ◽  
Skin Development ◽  
Epidermal Growth ◽  
Presenilin 2 ◽  
Polarized Exocytosis

How primary cilia impact epidermal growth and differentiation during embryogenesis is poorly understood. Here, we show that during skin development, Notch signaling occurs within the ciliated, differentiating cells of the first few suprabasal epidermal layers. Moreover, both Notch signaling and cilia disappear in the upper layers, where key ciliary proteins distribute to cell–cell borders. Extending this correlation, we find that Presenilin-2 localizes to basal bodies/cilia through a conserved VxPx motif. When this motif is mutated, a GFP-tagged Presenilin-2 still localizes to intercellular borders, but basal body localization is lost. Notably, in contrast to wild type, this mutant fails to rescue epidermal differentiation defects seen upon Psen1 and 2 knockdown. Screening components implicated in ciliary targeting and polarized exocytosis, we provide evidence that the small GTPase ARF4 is required for Presenilin basal body localization, Notch signaling, and subsequent epidermal differentiation. Collectively, our findings raise the possibility that ARF4-dependent polarized exocytosis acts through the basal body–ciliary complex to spatially regulate Notch signaling during epidermal differentiation.

scholarly journals Induction of Ran GTP drives ciliogenesis

2011 ◽  
Vol 22 (23) ◽  
pp. 4539-4548 ◽  
Author(s):  
Shuling Fan ◽  
Eileen L. Whiteman ◽  
Toby W. Hurd ◽  
Jeremy C. McIntyre ◽  
John F. Dishinger ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Protein Transport ◽  
Nucleocytoplasmic Transport ◽  
Small Gtpase ◽  
Basal Bodies ◽  
Ciliary Protein ◽  
Cilia Formation ◽  
Ran Gtp ◽  
New Evidence ◽  
Gtpase Ran

The small GTPase Ran and the importin proteins regulate nucleocytoplasmic transport. New evidence suggests that Ran GTP and the importins are also involved in conveying proteins into cilia. In this study, we find that Ran GTP accumulation at the basal bodies is coordinated with the initiation of ciliogenesis. The Ran-binding protein 1 (RanBP1), which indirectly accelerates Ran GTP → Ran GDP hydrolysis and promotes the dissociation of the Ran/importin complex, also localizes to basal bodies and cilia. To confirm the crucial link between Ran GTP and ciliogenesis, we manipulated the levels of RanBP1 and determined the effects on Ran GTP and primary cilia formation. We discovered that RanBP1 knockdown results in an increased concentration of Ran GTP at basal bodies, leading to ciliogenesis. In contrast, overexpression of RanBP1 antagonizes primary cilia formation. Furthermore, we demonstrate that RanBP1 knockdown disrupts the proper localization of KIF17, a kinesin-2 motor, at the distal tips of primary cilia in Madin–Darby canine kidney cells. Our studies illuminate a new function for Ran GTP in stimulating cilia formation and reinforce the notion that Ran GTP and the importins play key roles in ciliogenesis and ciliary protein transport.

scholarly journals BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis

2016 ◽  
Vol 36 (21) ◽  
pp. 2668-2680 ◽  
Author(s):  
Feng-Qian Li ◽  
Xingwang Chen ◽  
Cody Fisher ◽  
Saul S. Siller ◽  
Klara Zelikman ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Cultured Cells ◽  
Sequence Similarity ◽  
Affinity Purification ◽  
Coiled Coil ◽  
Lipid Binding ◽  
Small Gtpase ◽  
Basal Bodies ◽  
Membrane Remodeling ◽  
Bar Domains

Chibby1 (Cby1) is a small, conserved coiled-coil protein that localizes to centrioles/basal bodies and plays a crucial role in the formation and function of cilia. During early stages of ciliogenesis, Cby1 is required for the efficient recruitment of small vesicles at the distal end of centrioles to facilitate basal body docking to the plasma membrane. Here, we identified family with sequence similarity 92, member A (FAM92A) and FAM92B, which harbor predicted lipid-binding BAR domains, as novel Cby1-interacting partners using tandem affinity purification and mass spectrometry. We found that in cultured cell lines, FAM92A colocalizes with Cby1 at the centrioles/basal bodies of primary cilia, while FAM92B is undetectable. In airway multiciliated cells, both FAM92A and -92B colocalize with Cby1 at the base of cilia. Notably, the centriolar localization of FAM92A and -92B depends largely on Cby1. Knockdown of FAM92A in RPE1 cells impairs ciliogenesis. Consistent with the membrane-remodeling properties of BAR domains, FAM92A and -92B in cooperation with Cby1 induce deformed membrane-like structures containing the small GTPase Rab8 in cultured cells. Our results therefore suggest that FAM92 proteins interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes.

scholarly journals Regulating the transition from centriole to basal body

2011 ◽  
Vol 193 (3) ◽  
pp. 435-444 ◽  
Author(s):  
Tetsuo Kobayashi ◽  
Brian D. Dynlacht
Keyword(s):  
Cell Cycle ◽  
Basal Body ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Basal Bodies ◽  
Spindle Poles ◽  
Shed Light

The role of centrioles changes as a function of the cell cycle. Centrioles promote formation of spindle poles in mitosis and act as basal bodies to assemble primary cilia in interphase. Stringent regulations govern conversion between these two states. Although the molecular mechanisms have not been fully elucidated, recent findings have begun to shed light on pathways that regulate the conversion of centrioles to basal bodies and vice versa. Emerging studies also provide insights into how defects in the balance between centrosome and cilia function could promote ciliopathies and cancer.

scholarly journals A Role for the Primary Cilium in Notch Signaling and Epidermal Differentiation during Skin Development

Cell ◽  
2011 ◽  
Vol 145 (7) ◽  
pp. 1129-1141 ◽  
Author(s):  
Ellen J. Ezratty ◽  
Nicole Stokes ◽  
Sophia Chai ◽  
Alok S. Shah ◽  
Scott E. Williams ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Primary Cilium ◽  
Epidermal Differentiation ◽  
Skin Development

Ciliary coordination in newt lung cells requires microtubule-based linkages between basal bodies: A correlative light and EM study

1992 ◽  
Vol 50 (1) ◽  
pp. 570-571
Author(s):  
Robert Hard ◽  
Gerald Rupp ◽  
Matthew L. Withiam-Leitch ◽  
Lisa Cardamone
Keyword(s):  
Basal Body ◽  
Untreated Control ◽  
Beat Frequency ◽  
Primary Cultures ◽  
Living Cells ◽  
Power Stroke ◽  
Ultrastructural Changes ◽  
Lung Cells ◽  
Basal Bodies ◽  
Ciliated Cells

In a coordinated field of beating cilia, the direction of the power stroke is correlated with the orientation of basal body appendages, called basal feet. In newt lung ciliated cells, adjacent basal feet are interconnected by cold-stable microtubules (basal MTs). In the present study, we investigate the hypothesis that these basal MTs stabilize ciliary distribution and alignment. To accomplish this, newt lung primary cultures were treated with the microtubule disrupting agent, Colcemid. In newt lung cultures, cilia normally disperse in a characteristic fashion as the mucociliary epithelium migrates from the tissue explant. Four arbitrary, but progressive stages of dispersion were defined and used to monitor this redistribution process. Ciliaiy beat frequency, coordination, and dispersion were assessed for 91 hrs in untreated (control) and treated cultures. When compared to controls, cilia dispersed more rapidly and ciliary coordination decreased markedly in cultures treated with Colcemid (2 mM). Correlative LM/EM was used to assess whether these effects of Colcemid were coupled to ultrastructural changes. Living cells were defined as having coordinated or uncoordinated cilia and then were processed for transmission EM.

scholarly journals Current Views on the Roles of O-Glycosylation in Controlling Notch-Ligand Interactions

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 309
Author(s):  
Wataru Saiki ◽  
Chenyu Ma ◽  
Tetsuya Okajima ◽  
Hideyuki Takeuchi
Keyword(s):  
Notch Signaling ◽  
100Th Anniversary ◽  
Notch Receptor ◽  
Notch Receptors ◽  
Evolutionarily Conserved ◽  
Future Challenges ◽  
Ligand Interactions ◽  
Epidermal Growth ◽  
Notch Activation ◽  
Human Specific

The 100th anniversary of Notch discovery in Drosophila has recently passed. The Notch is evolutionarily conserved from Drosophila to humans. The discovery of human-specific Notch genes has led to a better understanding of Notch signaling in development and diseases and will continue to stimulate further research in the future. Notch receptors are responsible for cell-to-cell signaling. They are activated by cell-surface ligands located on adjacent cells. Notch activation plays an important role in determining the fate of cells, and dysregulation of Notch signaling results in numerous human diseases. Notch receptors are primarily activated by ligand binding. Many studies in various fields including genetics, developmental biology, biochemistry, and structural biology conducted over the past two decades have revealed that the activation of the Notch receptor is regulated by unique glycan modifications. Such modifications include O-fucose, O-glucose, and O-N-acetylglucosamine (GlcNAc) on epidermal growth factor-like (EGF) repeats located consecutively in the extracellular domain of Notch receptors. Being fine-tuned by glycans is an important property of Notch receptors. In this review article, we summarize the latest findings on the regulation of Notch activation by glycosylation and discuss future challenges.

scholarly journals Dominant Enhancers of Egfr in Drosophila melanogaster: Genetic Links Between the Notch and Egfr Signaling Pathways

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1139-1153 ◽  
Author(s):  
James V Price ◽  
Edward D Savenye ◽  
David Lum ◽  
Ashton Breitkreutz
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Growth Factor Receptor ◽  
Compound Eyes ◽  
Egfr Signaling ◽  
Wing Vein ◽  
Developmental Context ◽  
Epidermal Growth ◽  
Hypomorphic Alleles ◽  
Complex Signaling

The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed and F1 screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context.

scholarly journals Centrin2 regulates CP110 removal in primary cilium formation

2015 ◽  
Vol 208 (6) ◽  
pp. 693-701 ◽  
Author(s):  
Suzanna L. Prosser ◽  
Ciaran G. Morrison
Keyword(s):  
Calcium Binding ◽  
Primary Cilia ◽  
Reverse Genetics ◽  
Cell Types ◽  
Serum Starvation ◽  
Basal Bodies ◽  
Cilium Formation ◽  
Cellular Quiescence ◽  
Retinal Pigmented Epithelial Cells

Primary cilia are antenna-like sensory microtubule structures that extend from basal bodies, plasma membrane–docked mother centrioles. Cellular quiescence potentiates ciliogenesis, but the regulation of basal body formation is not fully understood. We used reverse genetics to test the role of the small calcium-binding protein, centrin2, in ciliogenesis. Primary cilia arise in most cell types but have not been described in lymphocytes. We show here that serum starvation of transformed, cultured B and T cells caused primary ciliogenesis. Efficient ciliogenesis in chicken DT40 B lymphocytes required centrin2. We disrupted CETN2 in human retinal pigmented epithelial cells, and despite having intact centrioles, they were unable to make cilia upon serum starvation, showing abnormal localization of distal appendage proteins and failing to remove the ciliation inhibitor CP110. Knockdown of CP110 rescued ciliation in CETN2-deficient cells. Thus, centrin2 regulates primary ciliogenesis through controlling CP110 levels.

Structural Analysis of Basal Bodies of The Isolated Oral Apparatus of Tetrahymena Pyriformis

1970 ◽  
Vol 6 (3) ◽  
pp. 679-700
Author(s):  
J. WOLFE
Keyword(s):  
Structural Analysis ◽  
Cell Membrane ◽  
Basal Body ◽  
Structural Integrity ◽  
Tetrahymena Pyriformis ◽  
Basal Plate ◽  
Basal Bodies ◽  
The Third ◽  
Ionic Detergent

The oral apparatus of Tetrahymena pyriformis was isolated using a non-ionic detergent to disrupt the cell membrane. The mouth consists largely of basal bodies and microfilaments. Each basal body is attached to the mouth by a basal plate which is integrated into the meshwork of microfilaments that confers upon the oral apparatus its structural integrity. Each basal body is composed of 9 triplet microtubules. Two of the 3 tubules, subfibres ‘A’ and ‘B’ are composed of filamentous rows of globules with a spacing of 4.5nm. The third tubule, subfibre ‘C’, is only one-third the length of the basal body.

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