scholarly journals Post-developmental extracellular proteoglycan maintenance in attractin-deficient mice

2020 ◽  
Author(s):  
Abdallah Azouz ◽  
Jonathan Duke-Cohan
Keyword(s):  
Extracellular Matrix ◽  
Brush Border ◽  
Intracellular Trafficking ◽  
Matrix Material ◽  
Secretory Vesicle ◽  
Secretory Vesicles ◽  
Kidney Tubules ◽  
Histochemical Analysis ◽  
Space Of Disse ◽  
Deficient Mice

Abstract Objective: Neurodegeneration and hair pigmentation alterations in mice occur consequent to aberrations at the Atrn locus coding for the transmembrane form of attractin. Earlier results pointed to a possible involvement in intracellular trafficking/export of secretory vesicles containing proteoglycan. Here we examined kidney and liver, both heavily dependent upon proteoglycan, of attractin-deficient mice to determine whether abnormalities were observed in these tissues.Results: Histological and histochemical analysis to detect glycosylated protein identified a severe loss in attractin-deficient mice of extracellular proteoglycan between kidney tubules in addition to a loss of glycosylated material within the intratubular brush border. In the liver, extracellular matrix material was significantly depleted between hepatocytes together with swollen sinuses and aberrations in the proteoglycan-dependent space of Disse. These results are consistent with a generalized defect in extracellular proteoglycan deposition in Atrn -mutant mice and support previous reports suggesting a role for attractin in the secretory vesicle pathway.

scholarly journals Sphingomyelin is sorted at the trans Golgi network into a distinct class of secretory vesicle

2016 ◽  
Vol 113 (24) ◽  
pp. 6677-6682 ◽  
Author(s):  
Yongqiang Deng ◽  
Felix E. Rivera-Molina ◽  
Derek K. Toomre ◽  
Christopher G. Burd
Keyword(s):  
Plasma Membrane ◽  
Intracellular Trafficking ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Secretory Vesicle ◽  
Secretory Protein ◽  
Secretory Vesicles ◽  
Distinct Class ◽  
Equinatoxin Ii ◽  
Golgi Network

One of the principal functions of the trans Golgi network (TGN) is the sorting of proteins into distinct vesicular transport carriers that mediate secretion and interorganelle trafficking. Are lipids also sorted into distinct TGN-derived carriers? The Golgi is the principal site of the synthesis of sphingomyelin (SM), an abundant sphingolipid that is transported. To address the specificity of SM transport to the plasma membrane, we engineered a natural SM-binding pore-forming toxin, equinatoxin II (Eqt), into a nontoxic reporter termed Eqt-SM and used it to monitor intracellular trafficking of SM. Using quantitative live cell imaging, we found that Eqt-SM is enriched in a subset of TGN-derived secretory vesicles that are also enriched in a glycophosphatidylinositol-anchored protein. In contrast, an integral membrane secretory protein (CD8α) is not enriched in these carriers. Our results demonstrate the sorting of native SM at the TGN and its transport to the plasma membrane by specific carriers.

scholarly journals Pig zona pellucida 2 (pZP2) protein does not participate in zona pellucida formation in transgenic mice

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 455-464 ◽  
Author(s):  
Akiko Hasegawa ◽  
Nozomi Kanazawa ◽  
Hideaki Sawai ◽  
Shinji Komori ◽  
Koji Koyama
Keyword(s):  
Extracellular Matrix ◽  
Transgenic Mice ◽  
Molecular Species ◽  
Zona Pellucida ◽  
Transgenic Protein ◽  
Specific Manner ◽  
Species Specific ◽  
Deficient Mice

The zona pellucida, an extracellular matrix surrounding mammalian oocytes, is composed of three or four glycoproteins. It is well known that the zona pellucida plays several critical roles during fertilization, but there is little knowledge about its formation. The purpose of this study is to examine whether a pig zona pellucida glycoprotein 2 (pZP2) would assemble with mouse zona pellucida. A transgene construct was prepared by placing a minigene encoding pZP2 downstream from the promoter of mouse ZP2. The result showed that the transgenic protein was synthesized in growing oocytes but not incorporated into the zona pellucida. Furthermore, the pZP2 transgene did not rescue the phenotype in ZP2-knockout zona-deficient mice. These results indicate that pZP2 does not participate in mouse zona pellucida formation and the zona pellucida is constituted from its component proteins in a molecular species-specific manner between mice and pigs.

Abstract 3863: Deletion Of Integrin Alpha7 Leads To Altered Cardiac Conduction And Sudden Death Associated With Connexin43 Downregulation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Raja Nadif ◽  
Michael Emerson ◽  
Ulrike Mayer ◽  
Ludwig Neyses ◽  
Elizabeth Cartwright
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Matrix ◽  
Ventricular Hypertrophy ◽  
Structural Changes ◽  
Cellular Adhesion ◽  
Left Ventricular ◽  
Cardiac Conduction ◽  
Cardiac Phenotype ◽  
One Year ◽  
Deficient Mice

Effective propagation of the electrical impulse throughout the myocardium is highly dependent on cell-to-cell and cell-to-extracellular matrix interactions. Increasing evidence indicates that dysregulation of cellular adhesion is a critical determinant in the genesis of arrhythmia. Null mutations in the integrin α7 gene, an essential mediator of cellular adhesion in cardiac and skeletal muscles, have been linked to myopathy in humans, however, the in vivo role of the integrin α7 subunit in the heart is undefined. The mouse model of integrin α7 deletion dies prematurely at one year of age. We therefore analysed the cardiac phenotype in integrin α7 deficient mice (α7 −/− ) to determine whether their premature death was associated with altered cardiac conduction. One year old integrin α7 −/− mice exhibited altered cardiac conduction characterised by spontaneous atrial fibrillation and prolonged QTc duration (α7 −/− : 25.7±0.74ms, α7 +/+ : 19.5±0.61ms; n=6; p<0.001, QTc=QT/(RR/100) 1/2 ). The abnormal cardiac conduction was associated with downregulation of connexin43. However, no significant changes were observed in the expression of ion chanels that have been linked to long QT syndrome or atrial fibrillation (kv1.1, kv1.5, kcne1, kcnq1, erg1, Cav1.2 and Cav1.3). In addition, α7 −/− mice displayed increased susceptibility to drug-induced arrhythmias: treatment with ouabain (2mg/kg BW) in combination with isoprenaline (2.5mg/kg BW) induced atrial fibrillation and ventricular tachycardia and eventually death in 6 month-old integrin α7 −/− mice, but not in α7 +/+ mice. Interestingly, α7 −/− also displayed concentric ventricular hypertrophy with increased septal wall thickness and reduced left ventricular end-diastolic diameter starting from 6 months of age. These structural changes were accompanied by an increase in myocyte size and increased ERK1/2 phosphorylation. In conclusion, deletion of the integrin α7 gene in mice leads to ventricular hypertrophy and to abnormal cardiac conduction. The integrin α7 deficient mice have a marked propensity to lethal arrhythmias through alterations in gap junctions but not ion channels. The integrin α7 knockout model provides new insight into the link between the extracellular matrix and cardiac conduction.

Synaptotagmin-1: A Multi-Functional Protein that Mediates Vesicle Docking, Priming, and Fusion

2021 ◽  
Vol 22 ◽  
Author(s):  
Najeeb Ullah ◽  
Ezzouhra El Maaiden ◽  
Md. Sahab Uddin ◽  
Ghulam Md Ashraf
Keyword(s):  
Plasma Membrane ◽  
Secretory Granules ◽  
Secretory Vesicle ◽  
Neuroendocrine Cells ◽  
Snare Complex ◽  
Secretory Vesicles ◽  
Functional Protein ◽  
Vesicle Docking ◽  
Synaptotagmin 1

: The fusion of secretory vesicles with the plasma membrane depends on the assembly of v-SNAREs (VAMP2/synaptobrevin2) and t-SNAREs (SNAP25/syntaxin1) into the SNARE complex. Vesicles go through several upstream steps, referred to as docking and priming, to gain fusion competence. The vesicular protein synaptotagmin-1 (Syt-1) is the principal Ca2+ sensor for fusion in several central nervous system neurons and neuroendocrine cells and part of the docking complex for secretory granules. Syt-1 binds to the acceptor complex such as synaxin1, SNAP-25 on the plasma membrane to facilitate secretory vesicle docking, and upon Ca2+-influx promotes vesicle fusion. This review assesses the role of the Syt-1 protein involved in the secretory vesicle docking, priming, and fusion.

scholarly journals The Cooh-Terminal Domain of Myo2p, a Yeast Myosin V, Has a Direct Role in Secretory Vesicle Targeting

1999 ◽  
Vol 147 (4) ◽  
pp. 791-808 ◽  
Author(s):  
Daniel Schott ◽  
Jackson Ho ◽  
David Pruyne ◽  
Anthony Bretscher
Keyword(s):  
Secretory Vesicle ◽  
Restrictive Temperature ◽  
Secretory Vesicles ◽  
Tail Domain ◽  
Myosin V ◽  
Direct Role ◽  
Rab Protein ◽  
Polarized Delivery ◽  
Actin Cables ◽  
Type V

MYO2 encodes a type V myosin heavy chain needed for the targeting of vacuoles and secretory vesicles to the growing bud of yeast. Here we describe new myo2 alleles containing conditional lethal mutations in the COOH-terminal tail domain. Within 5 min of shifting to the restrictive temperature, the polarized distribution of secretory vesicles is abolished without affecting the distribution of actin or the mutant Myo2p, showing that the tail has a direct role in vesicle targeting. We also show that the actin cable–dependent translocation of Myo2p to growth sites does not require secretory vesicle cargo. Although a fusion protein containing the Myo2p tail also concentrates at growth sites, this accumulation depends on the polarized delivery of secretory vesicles, implying that the Myo2p tail binds to secretory vesicles. Most of the new mutations alter a region of the Myo2p tail conserved with vertebrate myosin Vs but divergent from Myo4p, the myosin V involved in mRNA transport, and genetic data suggest that the tail interacts with Smy1p, a kinesin homologue, and Sec4p, a vesicle-associated Rab protein. The data support a model in which the Myo2p tail tethers secretory vesicles, and the motor transports them down polarized actin cables to the site of exocytosis.

scholarly journals Signature-Tagged Mutagenesis of Klebsiella pneumoniae To Identify Genes That Influence Biofilm Formation on Extracellular Matrix Material

2006 ◽  
Vol 74 (8) ◽  
pp. 4590-4597 ◽  
Author(s):  
Jennifer D. Boddicker ◽  
Rebecca A. Anderson ◽  
Jennifer Jagnow ◽  
Steven Clegg
Keyword(s):  
Extracellular Matrix ◽  
Klebsiella Pneumoniae ◽  
Biofilm Formation ◽  
Matrix Material ◽  
Infection Process ◽  
Bladder Epithelium ◽  
Tract Infections ◽  
Type 3

ABSTRACT Klebsiella pneumoniae causes urinary tract infections, respiratory tract infections, and septicemia in susceptible individuals. Strains of Klebsiella frequently produce extended-spectrum beta-lactamases, and infections with these strains can lead to relatively high mortality rates (approximately 15%). Other virulence factors include production of an antiphagocytic capsule and outer membrane lipopolysaccharide (LPS), which mediates serum resistance, as well as fimbriae on the surface of the bacteria. Type 1 fimbriae mediate adherence to many types of epithelial cells and may facilitate adherence of the bacteria to the bladder epithelium. Type 3 fimbriae can bind in vitro to the extracellular matrix of urinary and respiratory tissues, suggesting that they mediate binding to damaged epithelial surfaces. In addition, type 3 fimbriae are required for biofilm formation by Klebsiella pneumoniae on plastics and human extracellular matrix; thus, they may facilitate the formation of treatment-resistant biofilm on indwelling plastic devices, such as catheters and endotracheal tubing. The presence of these devices may cause tissue damage, allowing Klebsiella to grow as a biofilm on exposed tissue basement membrane components. Though in vivo biofilm growth may be an important step in the infection process, little is known about the genetic factors required for biofilm formation by Klebsiella pneumoniae. Thus, we performed signature-tagged mutagenesis to identify factors produced by K. pneumoniae strain 43816 that are required for biofilm formation. We identified mutations in the cps capsule gene cluster, previously unidentified transcriptional regulators, fimbrial, and sugar phosphotransferase homologues, as well as genetic loci of unknown function, that affect biofilm formation.

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