Role of the N-terminal transmembrane domain in the endo-lysosomal targeting and function of the human ABCB6 protein

The intracellular localization of ATP-binding cassette, sub family B (ABCB) 6 is a matter of debate. We show that ABCB6 is internalized from the plasma membrane to multivesicular bodies and lysosomes. Molecular dissection of the ABCB6 protein reveals a role of its N-terminal domain in targeting.

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Role of Exosomes in the Exchange of Spermatozoa after Leaving the Seminiferous Tubule: A Review

Current Drug Metabolism ◽

10.2174/1389200221666200520091511 ◽

2020 ◽

Vol 21 (5) ◽

pp. 330-338

Author(s):

Luming Wu ◽

Yuan Ding ◽

Shiqiang Han ◽

Yiqing Wang

Keyword(s):

Drug Delivery ◽

Plasma Membrane ◽

Seminiferous Tubule ◽

Metabolic Diseases ◽

Inflammatory Diseases ◽

Multivesicular Bodies ◽

Extensive Search ◽

Neurological Research ◽

The One

Background: Exosomes are extracellular vesicles (EVs) released from cells upon fusion of an intermediate endocytic compartment with the plasma membrane. They refer to the intraluminal vesicles released from the fusion of multivesicular bodies with the plasma membrane. The contents and number of exosomes are related to diseases such as metabolic diseases, cancer and inflammatory diseases. Exosomes have been used in neurological research as a drug delivery tool and also as biomarkers for diseases. Recently, exosomes were observed in the seminal plasma of the one who is asthenozoospermia, which can affect sperm motility and capacitation. Objective: The main objective of this review is to deeply discuss the role of exosomes in spermatozoa after leaving the seminiferous tubule. Methods: We conducted an extensive search of the literature available on relationships between exosomes and exosomes in spermatozoa on the bibliographic database. Conclusion: : This review thoroughly discussed the role that exosomes play in the exchange of spermatozoa after leaving the seminiferous tubule and its potential as a drug delivery tool and biomarkers for diseases as well.

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The role of the polar, carboxyl-terminal domain of Escherichia coli leader peptidase in its translocation across the plasma membrane.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)67097-8 ◽

1986 ◽

Vol 261 (29) ◽

pp. 13844-13849 ◽

Cited By ~ 2

Author(s):

R E Dalbey ◽

W Wickner

Keyword(s):

Escherichia Coli ◽

Plasma Membrane ◽

Terminal Domain ◽

Carboxyl Terminal Domain ◽

Carboxyl Terminal ◽

Leader Peptidase

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Extracellular vesicle interplay in cardiovascular pathophysiology

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00925.2020 ◽

2021 ◽

Author(s):

Sherin Saheera ◽

Vivek P Jani ◽

Kenneth W Witwer ◽

Shelby Kutty

Keyword(s):

Plasma Membrane ◽

Cardiovascular System ◽

Lipid Bilayer ◽

Cellular Responses ◽

Extracellular Vesicle ◽

Cargo Proteins ◽

And Function ◽

Intercellular Communications ◽

Rna And Dna

Extracellular vesicles (EVs) are nanosized lipid bilayer-delimited particles released from cells that mediate intercellular communications and play a pivotal role in various physiological and pathological processes. Subtypes of EVs may include plasma-membrane ectosomes or microvesicles and endosomal-origin exosomes, although functional distinctions remain unclear. EVs carry cargo proteins, nucleic acids (RNA and DNA), lipids, and metabolites. By presenting or transferring this cargo to recipient cells, EVs can trigger cellular responses. Here, we summarize what is known about EV biogenesis, composition, and function, with an emphasis on the role of EVs in cardiovascular system. Additionally, we provide an update on the function of EVs in cardiovascular pathophysiology, further highlighting their potential for diagnostic and therapeutic applications.

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Role of the ATP-Binding Cassette TransporterAbcg2in the Phenotype and Function of Cardiac Side Population Cells

Circulation Research ◽

10.1161/circresaha.108.174615 ◽

2008 ◽

Vol 103 (8) ◽

pp. 825-835 ◽

Cited By ~ 99

Author(s):

Otmar Pfister ◽

Angelos Oikonomopoulos ◽

Konstantina-Ioanna Sereti ◽

Regina L. Sohn ◽

Darragh Cullen ◽

...

Keyword(s):

Side Population ◽

Atp Binding ◽

Side Population Cells ◽

And Function ◽

Atp Binding Cassette

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Structure and Function of Membranes and the Role of the Plasma Membrane in Metabolic Regulations

Surface Membrane Receptors ◽

10.1007/978-1-4684-2772-1_2 ◽

1976 ◽

pp. 25-38

Author(s):

Efraim Racker

Keyword(s):

Plasma Membrane ◽

Structure And Function ◽

And Function

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The role of prolines and glycine in the transmembrane domain of LAT

10.1101/2020.08.10.244251 ◽

2020 ◽

Cited By ~ 1

Author(s):

Daniela Glatzová ◽

Harsha Mavila ◽

Maria Chiara Saija ◽

Tomáš Chum ◽

Lukasz Cwiklik ◽

...

Keyword(s):

Amino Acids ◽

Plasma Membrane ◽

Transmembrane Domain ◽

Transmembrane Helix ◽

Helical Structure ◽

Surface Expression ◽

Transmembrane Segment ◽

Proline Residue ◽

And Function ◽

The Impact

ABSTRACTLAT is a critical regulator of T cell development and function. It organises signalling events at the plasma membrane. However, the mechanism, which controls LAT localisation at the plasma membrane is not fully understood. Here, we studied the impact of helix-breaking amino acids, two prolines and one glycine, in the transmembrane segment on localisation and function of LAT. Using in silico analysis, confocal and superresolution imaging and flow cytometry we demonstrate that central proline residue destabilises transmembrane helix by inducing a kink. The helical structure and dynamics is further regulated by glycine and another proline residue in the luminal part of LAT transmembrane domain. Replacement of these residues with aliphatic amino acids reduces LAT dependence on palmitoylation for sorting to the plasma membrane. However, surface expression of these mutants is not sufficient to recover function of non-palmitoylated LAT in stimulated T cells. These data indicate that geometry and dynamics of LAT transmembrane segment regulate its localisation and function in immune cells.

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Roles of the cytoplasmic and transmembrane domains of syntaxins in intracellular localization and trafficking

Journal of Cell Science ◽

10.1242/jcs.114.17.3115 ◽

2001 ◽

Vol 114 (17) ◽

pp. 3115-3124 ◽

Cited By ~ 1

Author(s):

Kazuo Kasai ◽

Kimio Akagawa

Keyword(s):

Plasma Membrane ◽

Transmembrane Domain ◽

Intracellular Localization ◽

Transmembrane Domains ◽

Cytoplasmic Domains ◽

Immunofluorescence Analysis ◽

Attachment Protein ◽

Transport Pathways ◽

Sensitive Factor ◽

Protein Receptors

Syntaxins are target-soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (t-SNAREs) involved in docking and fusion of vesicles in exocytosis and endocytosis. Many syntaxin isoforms have been isolated, and each one displays a distinct intracellular localization pattern. However, the signals that drive the specific intracellular localization of syntaxins are poorly understood. In this study, we used indirect immunofluorescence analysis to examine the localization of syntaxin chimeras, each containing a syntaxin transmembrane domain fused to a cytoplasmic domain derived from a different syntaxin. We show that the cytoplasmic domains of syntaxins 5, 6, 7 and 8 have important effects on intracellular localization. We also demonstrate that the transmembrane domain of syntaxin 5 is sufficient to localize the chimera to the compartment expected for wild-type syntaxin 5. Additionally, we find that syntaxins 6, 7 and 8, but not syntaxin 5, are present at the plasma membrane, and that these syntaxins cycle through the plasma membrane by virtue of their cytoplasmic domains. Finally, we find that di-leucine-based motifs in the cytoplasmic domains of syntaxins 7 and 8 are necessary for their intracellular localization and trafficking via distinct transport pathways. Combined, these results suggest that both the cytoplasmic and the transmembrane domains play important roles in intracellular localization and trafficking of syntaxins.

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Functional characterization of the non-catalytic ectodomains of the nucleotide pyrophosphatase/phosphodiesterase NPP1

Biochemical Journal ◽

10.1042/bj20021943 ◽

2003 ◽

Vol 371 (2) ◽

pp. 321-330 ◽

Cited By ~ 38

Author(s):

Rik GIJSBERS ◽

Hugo CEULEMANS ◽

Mathieu BOLLEN

Keyword(s):

Catalytic Activity ◽

Catalytic Domain ◽

Transmembrane Domain ◽

Functional Characterization ◽

Structure Stability ◽

Subunit Structure ◽

Terminal Domain ◽

Nucleotide Pyrophosphatase ◽

Domain Truncation ◽

And Function

The ubiquitous nucleotide pyrophosphatases/phosphodiesterases NPP1–3 consist of a short intracellular N-terminal domain, a single transmembrane domain and a large extracellular part, comprising two somatomedin-B-like domains, a catalytic domain and a poorly defined C-terminal domain. We show here that the C-terminal domain of NPP1–3 is structurally related to a family of DNA/RNA non-specific endonucleases. However, none of the residues that are essential for catalysis by the endonucleases are conserved in NPP1–NPP3, suggesting that the nuclease-like domain of NPP1–3 does not represent a second catalytic domain. Truncation analysis revealed that the nuclease-like domain of NPP1 is required for protein stability, for the targeting of NPP1 to the plasma membrane and for the expression of catalytic activity. We also demonstrate that 16 conserved cysteines in the somatomedin-B-like domains of NPP1, in concert with two flanking cysteines, mediate the dimerization of NPP1. The K173Q polymorphism of NPP1, which maps to the second somatomedin-B-like domain and has been associated with the aetiology of insulin resistance, did not affect the dimerization or catalytic activity of NPP1, and did not endow NPP1 with an affinity for the insulin receptor. Our data suggest that the non-catalytic ectodomains contribute to the subunit structure, stability and function of NPP1–3.

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Establishing the role of PLVAP in protein-losing enteropathy: a homozygous missense variant leads to an attenuated phenotype

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105299 ◽

2018 ◽

Vol 55 (11) ◽

pp. 779-784 ◽

Cited By ~ 6

Author(s):

Alina Kurolap ◽

Orly Eshach-Adiv ◽

Claudia Gonzaga-Jauregui ◽

Katya Dolnikov ◽

Adi Mory ◽

...

Keyword(s):

Barrier Function ◽

Protein Function ◽

Transmembrane Domain ◽

Autosomal Recessive Inheritance ◽

Missense Variant ◽

Protein Loss ◽

Protein Losing Enteropathy ◽

Family Based ◽

And Function

BackgroundIntestinal integrity is essential for proper nutrient absorption and tissue homeostasis, with damage leading to enteric protein loss, that is, protein-losing enteropathy (PLE). Recently, homozygous nonsense variants in the plasmalemma vesicle-associated protein gene (PLVAP) were reported in two patients with severe congenital PLE. PLVAP is the building block of endothelial cell (EC) fenestral diaphragms; its importance in barrier function is supported by mouse models of Plvap deficiency.ObjectiveTo genetically diagnose two first-degree cousins once removed, who presented with PLE at ages 22 and 2.5 years.MethodsFamily-based whole exome sequencing was performed based on an autosomal recessive inheritance model. In silico analyses were used to predict variant impact on protein structure and function.ResultsWe identified a rare homozygous variant (NM_031310.2:c.101T>C;p.Leu34Pro) in PLVAP, which co-segregated with the disease. Leu34 is predicted to be located in a highly conserved, hydrophobic, α-helical region within the protein’s transmembrane domain, suggesting Leu34Pro is likely to disrupt protein function and/or structure. Electron microscopy and PLVAP immunohistochemistry demonstrated apparently normal diaphragm morphology, predicted to be functionally affected.ConclusionsBiallelic missense variants in PLVAP can cause an attenuated form of the PLE and hypertriglyceridaemia syndrome. Our findings support the role of PLVAP in the pathophysiology of PLE, expand the phenotypic and mutation spectrums and underscore PLVAP’s importance in EC barrier function in the gut.

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