frizzled regulates mirror-symmetric pattern formation in the Drosophila eye

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 3045-3055 ◽  
Author(s):  
L. Zheng ◽  
J. Zhang ◽  
R.W. Carthew
Keyword(s):  
Pattern Formation ◽  
Cell Surface ◽  
Transmembrane Protein ◽  
Photoreceptor Cells ◽  
Mirror Image ◽  
Morphogenetic Furrow ◽  
Symmetric Pattern ◽  
Mosaic Analysis ◽  
Drosophila Eye ◽  
A Cell

Coordinated morphogenesis of ommatidia during Drosophila eye development establishes a mirror-image symmetric pattern across the entire eye bisected by an anteroposterior equator. We have investigated the mechanisms by which this pattern formation occurs and our results suggest that morphogenesis is coordinated by a graded signal transmitted bidirectionally from the presumptive equator to the dorsal and ventral poles. This signal is mediated by frizzled, which encodes a cell surface transmembrane protein. Mosaic analysis indicates that frizzled acts non-autonomously in an equatorial to polar direction. It also indicates that relative levels of frizzled in photoreceptor cells R3 and R4 of each ommatidium affect their positional fate choices such that the cell with greater frizzled activity becomes an R3 cell and the cell with less frizzled activity becomes an R4 cell. Moreover, this bias affects the choice an ommatidium makes as to which direction to rotate. Equator-outwards progression of elav expression and expression of the nemo gene in the morphogenetic furrow are regulated by frizzled, which itself is dynamically expressed about the morphogenetic furrow. We propose that frizzled mediates a bidirectional signal emanating from the equator.

scholarly journals A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase

2017 ◽  
Vol 292 (18) ◽  
pp. 7304-7313 ◽  
Author(s):  
Hayato Yamamoto ◽  
Yuki Tobisawa ◽  
Toshihiro Inubushi ◽  
Fumitoshi Irie ◽  
Chikara Ohyama ◽  
...  
Keyword(s):  
Cell Surface ◽  
Dermatan Sulfate ◽  
Transmembrane Protein ◽  
Live Cells ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Ph Optimum ◽  
Hyaluronidase Activity ◽  
A Cell ◽  
Intermediate Size

Hyaluronan (HA) is an extremely large polysaccharide (glycosaminoglycan) involved in many cellular functions. HA catabolism is thought to involve the initial cleavage of extracellular high-molecular-weight (HMW) HA into intermediate-size HA by an extracellular or cell-surface hyaluronidase, internalization of intermediate-size HA, and complete degradation into monosaccharides in lysosomes. Despite considerable research, the identity of the hyaluronidase responsible for the initial HA cleavage in the extracellular space remains elusive. HYAL1 and HYAL2 have properties more consistent with lysosomal hyaluronidases, whereas CEMIP/KIAA1199, a recently identified HA-binding molecule that has HA-degrading activity, requires the participation of the clathrin-coated pit pathway of live cells for HA degradation. Here we show that transmembrane protein 2 (TMEM2), a mammalian homolog of a protein playing a role in zebrafish endocardial cushion development, is a cell-surface hyaluronidase. Live immunostaining and surface biotinylation assays confirmed that mouse TMEM2 is expressed on the cell surface in a type II transmembrane topology. TMEM2 degraded HMW-HA into ∼5-kDa fragments but did not cleave chondroitin sulfate or dermatan sulfate, indicating its specificity to HA. The hyaluronidase activity of TMEM2 was Ca2+-dependent; the enzyme's pH optimum is around 6–7, and unlike CEMIP/KIAA1199, TMEM2 does not require the participation of live cells for its hyaluronidase activity. Moreover, TMEM2-expressing cells could eliminate HA immobilized on a glass surface in a contact-dependent manner. Together, these data suggest that TMEM2 is the long-sought-after hyaluronidase that cleaves extracellular HMW-HA into intermediate-size fragments before internalization and degradation in the lysosome.

Hedgehog is an indirect regulator of morphogenetic furrow progression in the Drosophila eye disc

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3233-3240 ◽  
Author(s):  
D.I. Strutt ◽  
M. Mlodzik
Keyword(s):  
Pattern Formation ◽  
Imaginal Disc ◽  
Morphogenetic Furrow ◽  
Anterior Edge ◽  
Eye Disc ◽  
Drosophila Eye ◽  
Eye Imaginal Disc ◽  
Inductive Signal ◽  
Rate Of Movement

Pattern formation in the eye imaginal disc of Drosophila occurs in a wave that moves from posterior to anterior. The anterior edge of this wave is marked by a contracted band of cells known as the morphogenetic furrow, behind which photoreceptors differentiate. The movement of the furrow is dependent upon the secretion of the signalling protein Hedgehog (Hh) by more posterior cells, and it has been suggested that Hh acts as an inductive signal to induce cells to enter a furrow fate and begin differentiation. To further define the role of Hh in this process, we have analysed clones of cells lacking the function of the smoothened (smo) gene, which is required for transduction of the Hh signal and allows the investigation of the autonomous requirement for hh signalling. These experiments demonstrate that the function of hh in furrow progression is indirect. Cells that cannot receive/transduce the Hh signal are still capable of entering a furrow fate and differentiating normally. However, hh is required to promote furrow progression and regulate its rate of movement across the disc, since the furrow is significantly delayed in smo clones.

scholarly journals Identification of the atypical cadherin FAT1 as a novel glypican-3 interacting protein in liver cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Panpan Meng ◽  
Yi-Fan Zhang ◽  
Wangli Zhang ◽  
Xin Chen ◽  
Tong Xu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Interacting Protein ◽  
Extracellular Signaling ◽  
Putative Receptor ◽  
Elevated Expression ◽  
A Cell ◽  
Receptor Tyrosine Phosphatase

AbstractGlypican-3 (GPC3) is a cell surface heparan sulfate proteoglycan that is being evaluated as an emerging therapeutic target in hepatocellular carcinoma (HCC). GPC3 has been shown to interact with several extracellular signaling molecules, including Wnt, HGF, and Hedgehog. Here, we reported a cell surface transmembrane protein (FAT1) as a new GPC3 interacting protein. The GPC3 binding region on FAT1 was initially mapped to the C-terminal region (Q14517, residues 3662-4181), which covered a putative receptor tyrosine phosphatase (RTP)-like domain, a Laminin G-like domain, and five EGF-like domains. Fine mapping by ELISA and flow cytometry showed that the last four EGF-like domains (residues 4013-4181) contained a specific GPC3 binding site, whereas the RTP domain (residues 3662-3788) and the downstream Laminin G-2nd EGF-like region (residues 3829-4050) had non-specific GPC3 binding. In support of their interaction, GPC3 and FAT1 behaved concomitantly or at a similar pattern, e.g. having elevated expression in HCC cells, being up-regulated under hypoxia conditions, and being able to regulate the expression of EMT-related genes Snail, Vimentin, and E-Cadherin and promoting HCC cell migration. Taken together, our study provides the initial evidence for the novel mechanism of GPC3 and FAT1 in promoting HCC cell migration.

Making waves: pattern formation by a cell-surface-associated signal

2005 ◽  
Vol 13 (6) ◽  
pp. 249-252 ◽  
Author(s):  
Angela Stevens ◽  
Lotte Søgaard-Andersen
Keyword(s):  
Pattern Formation ◽  
Cell Surface ◽  
A Cell

A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: Ramifications for the complex physiology of TNF

Cell ◽  
1988 ◽  
Vol 53 (1) ◽  
pp. 45-53 ◽  
Author(s):  
M. Kriegler ◽  
C. Perez ◽  
K. DeFay ◽  
I. Albert ◽  
S.D. Lu
Keyword(s):  
Cell Surface ◽  
Transmembrane Protein ◽  
A Cell

The sidekick gene, a member of the immunoglobulin superfamily, is required for pattern formation in the Drosophila eye

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3303-3312 ◽  
Author(s):  
D.N. Nguyen ◽  
Y. Liu ◽  
M.L. Litsky ◽  
R. Reinke
Keyword(s):  
Temporal Order ◽  
Transmembrane Domain ◽  
Photoreceptor Cells ◽  
Cell Interaction ◽  
Immunoglobulin Superfamily ◽  
Eye Disc ◽  
Mosaic Analysis ◽  
Drosophila Eye ◽  
Undifferentiated Cells ◽  
Eye Imaginal Disc

In the Drosophila eye imaginal disc the photoreceptor cells (R cells) differentiate according to a precise spatial and temporal order. The sidekick (sdk) gene is necessary to prevent extra R cells from differentiating during eye disc development. The extra cell appears between R3 and R4 early in R cell clusters and is most likely the result of the mystery cell inappropriately differentiating as an R cell. Mosaic analysis shows that sdk is required neither in the R cells nor in the extra cell, suggesting that sdk is necessary in the surrounding undifferentiated cells. The sdk gene codes for a protein that is a member of the immunoglobulin superfamily, having six immunoglobulin domains, thirteen fibronectin repeats and a transmembrane domain. The protein structure is consistent with its participation in cell-cell interaction during eye development.

The beginning of pattern formation in the Drosophila compound eye: the morphogenetic furrow and the second mitotic wave

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 841-850 ◽  
Author(s):  
T. Wolff ◽  
D.F. Ready
Keyword(s):  
Pattern Formation ◽  
Lead Sulfide ◽  
Compound Eye ◽  
Eye Development ◽  
Periodic Pattern ◽  
Cell Analysis ◽  
Morphogenetic Furrow ◽  
Early Stages ◽  
Mitotic Wave ◽  
A Cell

Events in the morphogenetic furrow set the stage for all subsequent compound eye development in Drosophila. The periodic pattern of the adult eye begins in the furrow with the spaced initiation of ommatidial rudiments, the preclusters. A wave of mitosis closely follows the furrow. A cell-by-cell analysis reveals details of these events. Early stages of ommatidial assembly can be resolved using a lead sulfide stain. Overt ommatidial organization begins in the morphogenetic furrow as cells gather into periodically spaced concentric aggregates. A stereotyped sequence of cell rearrangements converts these aggregates into preclusters. In the furrow, new rows of ommatidia are initiated at the equator and grow as new clusters are added to the peripheral ends. Mitotic labeling using BrdU feeds shows that all cells not incorporated into a precluster divide. BrdU injections show that cells divide roughly simultaneously between two adjacent rows of ommatidia.

Mechanisms of Signaling through Urokinase Receptor and the Cellular Response

1999 ◽  
Vol 82 (08) ◽  
pp. 305-311 ◽  
Author(s):  
Yuri Koshelnick ◽  
Monika Ehart ◽  
Hannes Stockinger ◽  
Bernd Binder
Keyword(s):  
Cell Surface ◽  
Proteolytic Activity ◽  
Tumor Invasion ◽  
Cellular Response ◽  
Transmembrane Protein ◽  
Urokinase Receptor ◽  
Biological Processes ◽  
In Vivo Models ◽  
Proteolytic Activation ◽  
Core Proteins

IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in a number of biological processes, including local fibrinolysis, tumor invasion, angiogenesis, neointima and atherosclerotic plaque formation, inflammation, and matrix remodeling during wound healing and development.1-6 Binding of urokinase to its specific receptor provides cells with a localized proteolytic potential. It stimulates conversion of cell surface-bound plasminogen into active plasmin, which, in turn, is required for proteolytic degradation of basement membrane components, including fibronectin, collagen, laminin, and proteoglycan core proteins.7 Moreover, plasmin activates other matrix-degrading enzymes, such as matrix metalloproteinases.8 Overexpression of u-PA/u-PAR correlates with tumor invasion and metastasis formation,9-13 while reduction of cell-surface bound u-PA and inhibition of u-PAR expression leads to a significant decrease of invasive and metastatic activity.14 Specific antagonists that suppress binding of u-PA to u-PAR have been shown to inhibit cell-surface plasminogen activation, tumor growth, and angiogenesis both in vitro and in vivo models.15,16 Independently of its proteolytic activity, u-PA is implicated in many biological processes that seem to require u-PAR-mediated intracellular signal transduction, such as proliferation, chemotactic movement and adhesion, migration, and differentiation.17 Data obtained in the late 1980s indicated that u-PA not only provides cells with local proteolytic activity, but might also be capable of transducing signals to the cell.18-22 At that time, however, the u-PAR has just been isolated, cloned, and identified as a glycosylphosphatidylinositol (GPI)-linked protein and not a transmembrane protein. Signaling via the u-PAR was, therefore, regarded as being unlikely, and the effects of u-PA on cell proliferation18-22 were thought to be mediated by proteolytic activation of latent growth factors. The assumption of direct signaling via u-PAR was, in fact, considered controversial, until about 10 years later when a physical association between u-PAR and signaling proteins was found.23 From this report on, several proteins associated with u-PAR have been identified. Now, u-PAR seems to be part of a large “signalosome” associated and interacting with several proteins on both the outside and inside of the cell.

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