scholarly journals Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis

2011 ◽  
Vol 194 (4) ◽  
pp. 631-642 ◽  
Author(s):  
Kaelyn D. Sumigray ◽  
Hsin Chen ◽  
Terry Lechler
Keyword(s):  
Cortical Microtubule ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Cell Cortex ◽  
Microtubule Organization ◽  
Specific Subset ◽  
Keratin Filaments ◽  
Perinatal Lethality ◽  
Cytoskeletal Networks ◽  
Centrosomal Proteins

Desmosomes are cell–cell adhesion structures that integrate cytoskeletal networks. In addition to binding intermediate filaments, the desmosomal protein desmoplakin (DP) regulates microtubule reorganization in the epidermis. In this paper, we identify a specific subset of centrosomal proteins that are recruited to the cell cortex by DP upon epidermal differentiation. These include Lis1 and Ndel1, which are centrosomal proteins that regulate microtubule organization and anchoring in other cell types. This recruitment was mediated by a region of DP specific to a single isoform, DPI. Furthermore, we demonstrate that the epidermal-specific loss of Lis1 results in dramatic defects in microtubule reorganization. Lis1 ablation also causes desmosomal defects, characterized by decreased levels of desmosomal components, decreased attachment of keratin filaments, and increased turnover of desmosomal proteins at the cell cortex. This contributes to loss of epidermal barrier activity, resulting in completely penetrant perinatal lethality. This work reveals essential desmosome-associated components that control cortical microtubule organization and unexpected roles for centrosomal proteins in epidermal function.

scholarly journals Control of cortical microtubule organization and desmosome stability by centrosomal proteins

2011 ◽  
Vol 1 (5) ◽  
pp. 221-224 ◽  
Author(s):  
Kaelyn D. Sumigray ◽  
Terry Lechler
Keyword(s):  
Cortical Microtubule ◽  
Microtubule Organization ◽  
Centrosomal Proteins

scholarly journals Regulation of epidermal differentiation by a Distal-less homeodomain gene.

1996 ◽  
Vol 135 (6) ◽  
pp. 1879-1887 ◽  
Author(s):  
M I Morasso ◽  
N G Markova ◽  
T D Sargent
Keyword(s):  
Cell Layer ◽  
Ectopic Expression ◽  
Single Layer ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Basal Cells ◽  
Basal Cell Layer ◽  
Suprabasal Cell ◽  
Important Regulator ◽  
Perinatal Lethality

The Distal-less-related homeodomain gene Dlx3 is expressed in terminally differentiated murine epidermal cells. Ectopic expression of this gene in the basal cell layer of transgenic skin results in a severely abnormal epidermal phenotype and leads to perinatal lethality. The basal cells of affected mice ceased to proliferate, and expressed the profilaggrin and loricrin genes which are normally transcribed only in the latest stages of epidermal differentiation. All suprabasal cell types were diminished and the stratum corneum was reduced to a single layer. These data indicate that Dlx3 misexpression results in transformation of basal cells into more differentiated keratinocytes, suggesting that this homeoprotein is an important regulator of epidermal differentiation.

scholarly journals Epidermal development requires ninein for spindle orientation and cortical microtubule organization

2019 ◽  
Vol 2 (2) ◽  
pp. e201900373 ◽  
Author(s):  
Nicolas Lecland ◽  
Chiung-Yueh Hsu ◽  
Cécile Chemin ◽  
Andreas Merdes ◽  
Christiane Bierkamp
Keyword(s):  
Progenitor Cells ◽  
Cortical Microtubule ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Microtubule Organization ◽  
Differentiation Markers ◽  
Epidermal Barrier ◽  
Skin Development ◽  
Protein Levels ◽  
Dependent Transport

In mammalian skin, ninein localizes to the centrosomes of progenitor cells and relocates to the cell cortex upon differentiation of keratinocytes, where cortical arrays of microtubules are formed. To examine the function of ninein in skin development, we use epidermis-specific and constitutive ninein-knockout mice to demonstrate that ninein is necessary for maintaining regular protein levels of the differentiation markers filaggrin and involucrin, for the formation of desmosomes, for the secretion of lamellar bodies, and for the formation of the epidermal barrier. Ninein-deficient mice are viable but develop a thinner skin with partly impaired epidermal barrier. We propose two underlying mechanisms: first, ninein contributes to spindle orientation during the division of progenitor cells, whereas its absence leads to misoriented cell divisions, altering the pool of progenitor cells. Second, ninein is required for the cortical organization of microtubules in differentiating keratinocytes, and for the cortical re-localization of microtubule-organizing proteins, and may thus affect any mechanisms that depend on localized microtubule-dependent transport.

scholarly journals Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

2019 ◽  
Author(s):  
Liu He ◽  
Robbelien Kooistra ◽  
Ravi Das ◽  
Ellen Oudejans ◽  
Eric V. van Leen ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Types ◽  
In Vivo Model ◽  
Cell Cortex ◽  
Neuronal Polarity ◽  
Microtubule Organization ◽  
Microtubule Cytoskeleton ◽  
Developmental Defects ◽  
Flow Through

SUMMARYNeurons are among the most highly polarized cell types. They possess structurally and functionally different processes, axon and dendrites, to mediate information flow through the nervous system. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is little understood.Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cell cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

scholarly journals Sas4 links basal bodies to cell division via Hippo signaling

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Marisa D. Ruehle ◽  
Alexander J. Stemm-Wolf ◽  
Chad G. Pearson
Keyword(s):  
Cell Division ◽  
Signaling Pathway ◽  
Cortical Microtubule ◽  
Cell Cortex ◽  
Basal Bodies ◽  
Hippo Signaling ◽  
Microtubule Organization ◽  
Hippo Signaling Pathway ◽  
Daughter Cells ◽  
Striated Fiber

Basal bodies (BBs) are macromolecular complexes required for the formation and cortical positioning of cilia. Both BB assembly and DNA replication are tightly coordinated with the cell cycle to ensure their accurate segregation and propagation to daughter cells, but the mechanisms ensuring coordination are unclear. The Tetrahymena Sas4/CPAP protein is enriched at assembling BBs, localizing to the core BB structure and to the base of BB-appendage microtubules and striated fiber. Sas4 is necessary for BB assembly and cortical microtubule organization, and Sas4 loss disrupts cell division furrow positioning and DNA segregation. The Hippo signaling pathway is known to regulate cell division furrow position, and Hippo molecules localize to BBs and BB-appendages. We find that Sas4 loss disrupts localization of the Hippo activator, Mob1, suggesting that Sas4 mediates Hippo activity by promoting scaffolds for Mob1 localization to the cell cortex. Thus, Sas4 links BBs with an ancient signaling pathway known to promote the accurate and symmetric segregation of the genome.

scholarly journals Linking cortical microtubule attachment and exocytosis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 469 ◽  
Author(s):  
Ivar Noordstra ◽  
Anna Akhmanova
Keyword(s):  
Targeted Delivery ◽  
Mammalian Cells ◽  
Spatial Organization ◽  
Protein Complexes ◽  
Cortical Microtubule ◽  
Actin Binding ◽  
Cell Cortex ◽  
Microtubule Organization ◽  
Vesicle Docking ◽  
Microtubule Attachment

Exocytosis is a fundamental cellular process whereby secreted molecules are packaged into vesicles that move along cytoskeletal filaments and fuse with the plasma membrane. To function optimally, cells are strongly dependent on precisely controlled delivery of exocytotic cargo. In mammalian cells, microtubules serve as major tracks for vesicle transport by motor proteins, and thus microtubule organization is important for targeted delivery of secretory carriers. Over the years, multiple microtubule-associated and cortical proteins have been discovered that facilitate the interaction between the microtubule plus ends and the cell cortex. In this review, we focus on mammalian protein complexes that have been shown to participate in both cortical microtubule capture and exocytosis, thereby regulating the spatial organization of secretion. These complexes include microtubule plus-end tracking proteins, scaffolding factors, actin-binding proteins, and components of vesicle docking machinery, which together allow efficient coordination of cargo transport and release.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

A Deficiency Screen for Zygotic Loci Required for Establishment and Patterning of the Epidermis in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 185-206 ◽  
Author(s):  
Rebecca M Terns ◽  
Peggy Kroll-Conner ◽  
Jiangwen Zhu ◽  
Sooyoun Chung ◽  
Joel H Rothman
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Epidermal Cells ◽  
Epidermal Differentiation ◽  
Apparent Effect ◽  
Internal Organs ◽  
C Elegans ◽  
Seam Cell ◽  
Genomic Regions ◽  
Caenorhabditis Elegans Genome

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least ∼67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

Microtubule organization across cell types and states

2021 ◽  
Vol 31 (10) ◽  
pp. R506-R511
Author(s):  
Maria D. Sallee ◽  
Jessica L. Feldman
Keyword(s):  
Cell Types ◽  
Microtubule Organization

scholarly journals NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Lindsey Seldin ◽  
Andrew Muroyama ◽  
Terry Lechler
Keyword(s):  
Cell Fate ◽  
Mitotic Spindle ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Spindle Orientation ◽  
Direct Function ◽  
Spindle Positioning ◽  
Adult Mice ◽  
Neonatal Lethality ◽  
The Matrix

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures.

Sign in / Sign up

Export Citation Format

Share Document