scholarly journals CLPTM1L is a lipid scramblase involved in glycosylphosphatidylinositol biosynthesis

2021 ◽  
Author(s):  
Yicheng Wang ◽  
Anant K. Menon ◽  
Yuta Maki ◽  
Yi-Shi Liu ◽  
Yugo Iwasaki ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Cultured Cells ◽  
Transmembrane Protein ◽  
Eukaryotic Cell ◽  
Surface Proteins ◽  
Cell Surface Proteins

Glycosylphosphatidylinositols (GPIs) are membrane anchors of many eukaryotic cell surface proteins. Biosynthesis of GPIs is initiated at the cytosolic face of the endoplasmic reticulum (ER) and the second intermediate, glucosaminyl-phosphatidylinositol (GlcN-PI), is translocated across the membrane to the lumenal face for later biosynthetic steps and attachment to proteins. The mechanism of the lumenal translocation of GlcN-PI is unclear. We report that Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L), an ER membrane protein of unknown function, is a lipid scramblase involved in GPI biosynthesis. Purified CLPTM1L scrambles GlcN-PI, PI, and several other phospholipids in vitro. Knockout of CLPTM1L gene in mammalian cultured cells partially decreased GPI-anchored proteins due to impaired usage of GlcN-PI, suggesting a major role of CLPTM1L in lumenal translocation of GlcN-PI.

scholarly journals Gaa1p and Gpi8p Are Components of a Glycosylphosphatidylinositol (GPI) Transamidase That Mediates Attachment of GPI to Proteins

2000 ◽  
Vol 11 (5) ◽  
pp. 1523-1533 ◽  
Author(s):  
Kazuhito Ohishi ◽  
Norimitsu Inoue ◽  
Yusuke Maeda ◽  
Junji Takeda ◽  
Howard Riezman ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Posttranslational Modification ◽  
Eukaryotic Cell ◽  
Surface Proteins ◽  
F9 Cells ◽  
Precursor Proteins ◽  
Key Enzyme ◽  
Gpi Transamidase

Many eukaryotic cell surface proteins are anchored to the membrane via glycosylphosphatidylinositol (GPI). The GPI is attached to proteins that have a GPI attachment signal peptide at the carboxyl terminus. The GPI attachment signal peptide is replaced by a preassembled GPI in the endoplasmic reticulum by a transamidation reaction through the formation of a carbonyl intermediate. GPI transamidase is a key enzyme of this posttranslational modification. Here we report that Gaa1p and Gpi8p are components of a GPI transamidase. To determine a role of Gaa1p we disrupted aGAA1/GPAA1 gene in mouse F9 cells by homologous recombination. GAA1 knockout cells were defective in the formation of carbonyl intermediates between precursor proteins and transamidase as determined by an in vitro GPI-anchoring assay. We also show that cysteine and histidine residues of Gpi8p, which are conserved in members of a cysteine protease family, are essential for generation of a carbonyl intermediate. This result suggests that Gpi8p is a catalytic component that cleaves the GPI attachment signal peptide. Moreover, Gaa1p and Gpi8p are associated with each other. Therefore, Gaa1p and Gpi8p constitute a GPI transamidase and cooperate in generating a carbonyl intermediate, a prerequisite for GPI attachment.

scholarly journals Highly Stoichiometric, Stable, and Specific Association of Integrin α3β1 with CD151 Provides a Major Link to Phosphatidylinositol 4-Kinase, and May Regulate Cell Migration

1998 ◽  
Vol 9 (10) ◽  
pp. 2751-2765 ◽  
Author(s):  
Robert L. Yauch ◽  
Fedor Berditchevski ◽  
Mary Beth Harler ◽  
Jonathan Reichner ◽  
Martin E. Hemler
Keyword(s):  
Cell Migration ◽  
Kinase Activity ◽  
Surface Proteins ◽  
Cell Surface Proteins ◽  
Α3β1 Integrin ◽  
Specific Association ◽  
Phosphatidylinositol 4 ◽  
Integrin Α3β1

Here we describe an association between α3β1 integrin and transmembrane-4 superfamily (TM4SF) protein CD151. This association is maintained in relatively stringent detergents and thus is remarkably stable in comparison with previously reported integrin–TM4SF protein associations. Also, the association is highly specific (i.e., observed in vitro in absence of any other cell surface proteins), and highly stoichiometric (nearly 90% of α3β1 associated with CD151). In addition, α3β1 and CD151 appeared in parallel on many cell lines and showed nearly identical skin staining patterns. Compared with other integrins, α3β1 exhibited a considerably higher level of associated phosphatidylinositol-4-kinase (PtdIns 4-kinase) activity, most of which was removed upon immunodepletion of CD151. Specificity for CD151 and PtdIns 4-kinase association resided in theextracellular domain of α3β1, thus establishing a novel paradigm for the specific recruitment of anintracellular signaling molecule. Finally, antibodies to either CD151 or α3β1 caused a ∼88–92% reduction in neutrophil motility in response to f-Met-Leu-Phe on fibronectin, suggesting an functionally important role of these complexes in cell migration.

scholarly journals Cell Surface Expression of Nrg1 Protein in Candida auris

2021 ◽  
Vol 7 (4) ◽  
pp. 262
Author(s):  
Anuja Paudyal ◽  
Govindsamy Vediyappan
Keyword(s):  
Cell Surface ◽  
Growth Conditions ◽  
Zinc Ion ◽  
Surface Proteins ◽  
Cell Surface Expression ◽  
Unexpected Finding ◽  
Candida Auris ◽  
Cell Surface Proteins ◽  
Biofilm Growth

Candida auris is an emerging antifungal resistant human fungal pathogen increasingly reported in healthcare facilities. It persists in hospital environments, and on skin surfaces, and can form biofilms readily. Here, we investigated the cell surface proteins from C. auris biofilms grown in a synthetic sweat medium mimicking human skin conditions. Cell surface proteins from both biofilm and planktonic control cells were extracted with a buffer containing β-mercaptoethanol and resolved by 2-D gel electrophoresis. Some of the differentially expressed proteins were excised and identified by mass spectrometry. C. albicans orthologs Spe3p, Tdh3p, Sod2p, Ywp1p, and Mdh1p were overexpressed in biofilm cells when compared to the planktonic cells of C. auris. Interestingly, several proteins with zinc ion binding activity were detected. Nrg1p is a zinc-binding transcription factor that negatively regulates hyphal growth in C. albicans. C. auris does not produce true hypha under standard in vitro growth conditions, and the role of Nrg1p in C. auris is currently unknown. Western blot analyses of cell surface and cytosolic proteins of C. auris against anti-CalNrg1 antibody revealed the Nrg1p in both locations. Cell surface localization of Nrg1p in C. auris, an unexpected finding, was further confirmed by immunofluorescence microscopy. Nrg1p expression is uniform across all four clades of C. auris and is dependent on growth conditions. Taken together, the data indicate that C. auris produces several unique proteins during its biofilm growth, which may assist in the skin-colonizing lifestyle of the fungus during its pathogenesis.

The role of external aetiological factors in dental anomalies in non-syndromic cleft lip and palate patients

2018 ◽  
Vol 20 (2) ◽  
pp. 105-111 ◽  
Author(s):  
M. V. Korolenkova ◽  
N. V. Starikova ◽  
N. V. Udalova
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Dental Anomalies

Dental Findings in Parents of Children with Cleft Lip and Palate

1996 ◽  
Vol 33 (5) ◽  
pp. 436-439 ◽  
Author(s):  
Peter J. Anderson ◽  
Anthony L.H., Moss
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Normal Population ◽  
Permanent Teeth ◽  
Dental Anomalies ◽  
Facial Skeleton ◽  
Missing Teeth ◽  
Congenitally Missing Teeth ◽  
Congenitally Missing

The incidence of dental abnormalities in the cleft lip and palate population has been reported to be much higher than in the normal population. The role of genes in the production of a cleft lip and palate, and dental anomalies is thought to be complex, with autosomal dominant, recessive, and x-linked genes all playing a role. Noncleft parents can carry some of the cleft lip and palate genes, which produce clinically subtle manifestations in their facial skeleton. The purpose of this study was to look for evidence of increased dental anomalies in the non-cleft parents of cleft lip and palate children. The dentitions of the parents of 60 children with different types of cleft lip and palate were examined prospectively to see whether or not they exhibited features found more readily in the cleft lip and palate rather than did the normal population. Their dentitions were studied to record the following dental features: congenitally missing teeth, supernumerary teeth, or morphologic changes of the crowns of the permanent teeth. The number and position of any frenal attachments were also recorded. The results of this study did not show any differences in incidence of dental anomalies from the noncleft population. There was no evidence to support the hypothesis that congenital absence of lateral incisors is a microform of cleft lip and palate. Further, these results also failed to reveal any consistent pattern in the number and position of frenal attachments.

scholarly journals SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shiyu Chen ◽  
Zhonglin Jia ◽  
Ming Cai ◽  
Mujie Ye ◽  
Dandan Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Chondrogenic Differentiation ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Tissue Sample ◽  
Human Umbilical Cord

Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/β-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/β-catenin signaling pathway.

scholarly journals The important role of MDM2, RPL5, and TP53 in mycophenolic acid-induced cleft lip and palate

Medicine ◽  
2021 ◽  
Vol 100 (21) ◽  
pp. e26101
Author(s):  
Yangyang Lin ◽  
Tao Song ◽  
Elsa M. Ronde ◽  
Gang Ma ◽  
Huiqin Cui ◽  
...  
Keyword(s):  
Mycophenolic Acid ◽  
Cleft Lip ◽  
Cleft Lip And Palate

scholarly journals ROLE OF A PEDODONTIST IN CLEFT LIP AND CLEFT PALATE REHABILITATION - AN OVERVIEW

2021 ◽  
Vol 9 (07) ◽  
pp. 882-906
Author(s):  
Payel Basu ◽  
◽  
Rani Somani ◽  
Deepti Jawa ◽  
Shipra Jaidka ◽  
...  
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Multidisciplinary Care ◽  
Vital Role ◽  
Pediatric Dentist ◽  
Orofacial Region ◽  
The Right ◽  
Potential Area

Cleft lip and palate is one of the most common congenital anomalies requiring multidisciplinary care. Such anomaly is associated with many problems such as impaired feeding, defective speech, hearing difficulties, malocclusion, dental abnormalities, gross facial deformity as well severe psychological problems. Cleft of the lip and palate is one of the complex conditions that occur at a functionally potential area in the orofacial region and also at such a crucial time that strategic interventions at the right age by the concerned specialists becomes the need of the hour. Pediatric dentist is an integral part of the cleft rehabilitative process right from the neonatal period upto the phase of permanent dentition. Being well versed with a childs growth and development, both physical and mental, a Pedodontist helps in restoring function and esthetics in a cleft child, in a most empathetic way. This article describes the enormous challenges faced by these innocent souls and the vital role played by a Pedodontist, to provide comprehensive cleft care, be it preventive, restorative, or interventional care, in order to achieve the best possible outcome and meaningfully improve their quality of life.

scholarly journals Immunosuppressive Mechanisms of Regulatory B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Catalán ◽  
Miguel Andrés Mansilla ◽  
Ashley Ferrier ◽  
Lilian Soto ◽  
Kristine Oleinika ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
Surface Proteins ◽  
Regulatory B Cells ◽  
Cell Surface Proteins ◽  
The Past ◽  
And Function

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

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