BP180/Collagen XVII: A Molecular View

BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer is a central component in type I hemidesmosomes (HD), which cause the adhesion between epidermal keratinocytes and the basal lamina, but BP180 is also expressed in several non-HD locations, where its functions are poorly characterized. The immunological roles of intact and proteolytically processed BP180, relevant in BP, have been subject to intensive research, but novel functions in cell proliferation, differentiation, and aging have also recently been described. To better understand the multiple physiological functions of BP180, the focus should return to the protein itself. Here, we comprehensively review the properties of the BP180 molecule, present new data on the biochemical features of its intracellular domain, and discuss their significance with regard to BP180 folding and protein–protein interactions.

Download Full-text

TRIM22. A Multitasking Antiviral Factor

Cells ◽

10.3390/cells10081864 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1864

Author(s):

Isabel Pagani ◽

Guido Poli ◽

Elisa Vicenzi

Keyword(s):

Protein Interactions ◽

Influenza A ◽

Direct Interaction ◽

Type I Interferons ◽

Viral Gene ◽

Target Cells ◽

Type I ◽

Protein Protein Interactions ◽

Viral Genomes ◽

Dna And Rna

Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.

Download Full-text

Expanded: a gene involved in the control of cell proliferation in imaginal discs

Development ◽

10.1242/dev.118.4.1291 ◽

1993 ◽

Vol 118 (4) ◽

pp. 1291-1301 ◽

Cited By ~ 15

Author(s):

M. Boedigheimer ◽

A. Laughon

Keyword(s):

Cell Proliferation ◽

Protein Interactions ◽

Essential Gene ◽

Spontaneous Mutation ◽

Growth Control ◽

Imaginal Discs ◽

Apical Surface ◽

Protein Protein Interactions ◽

Acid Protein ◽

Disc Cells

The expanded gene was first identified by a spontaneous mutation that causes broad wings. We have identified an enhancer-trap insertion within expanded and used it to generate additional mutations, including one null allele. expanded is an essential gene, necessary for proper growth control of imaginal discs and, when mutant, causes either hyperplasia or degeneration depending on the disc. Wing overgrowth in expanded hypermorphs is limited to specific regions along the anterior-posterior and dorsal-ventral axis. expanded encodes a novel 1429 amino acid protein that is localized to the apical surface of disc cells and contains three potential SH3-binding sites. Together, these observations suggest that the Expanded protein engages in protein-protein interactions regulating cell proliferation in discs.

Download Full-text

Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1918807117 ◽

2020 ◽

Vol 117 (6) ◽

pp. 2968-2977

Author(s):

Zhiyu Liu ◽

Herong Shi ◽

Anthony K. Nzessi ◽

Anne Norris ◽

Barth D. Grant ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Cell Surface ◽

Molecular Mechanisms ◽

Transmembrane Protein ◽

Expression Patterns ◽

Bmp Signaling ◽

Type I ◽

Type Ii ◽

Bmp Receptors

Tetraspanins are a unique family of 4-pass transmembrane proteins that play important roles in a variety of cell biological processes. We have previously shown that 2 paralogous tetraspanins in Caenorhabditis elegans, TSP-12 and TSP-14, function redundantly to promote bone morphogenetic protein (BMP) signaling. The underlying molecular mechanisms, however, are not fully understood. In this study, we examined the expression and subcellular localization patterns of endogenously tagged TSP-12 and TSP-14 proteins. We found that TSP-12 and TSP-14 share overlapping expression patterns in multiple cell types, and that both proteins are localized on the cell surface and in various types of endosomes, including early, late, and recycling endosomes. Animals lacking both TSP-12 and TSP-14 exhibit reduced cell-surface levels of the BMP type II receptor DAF-4/BMPRII, along with impaired endosome morphology and mislocalization of DAF-4/BMPRII to late endosomes and lysosomes. These findings indicate that TSP-12 and TSP-14 are required for the recycling of DAF-4/BMPRII. Together with previous findings that the type I receptor SMA-6 is recycled via the retromer complex, our work demonstrates the involvement of distinct recycling pathways for the type I and type II BMP receptors and highlights the importance of tetraspanin-mediated intracellular trafficking in the regulation of BMP signaling in vivo. As TSP-12 and TSP-14 are conserved in mammals, our findings suggest that the mammalian TSP-12 and TSP-14 homologs may also function in regulating transmembrane protein recycling and BMP signaling.

Download Full-text

An activity-based probe reveals dynamic protein–protein interactions mediating IGF-1R transactivation by the GABAB receptor

Biochemical Journal ◽

10.1042/bj20120188 ◽

2012 ◽

Vol 443 (3) ◽

pp. 627-634 ◽

Cited By ~ 17

Author(s):

Xin Lin ◽

Xin Li ◽

Ming Jiang ◽

Linhai Chen ◽

Chanjuan Xu ◽

...

Keyword(s):

Protein Interactions ◽

Protein Complex ◽

Tyrosine Kinases ◽

Chemical Biology ◽

Molecular Mechanisms ◽

Gabab Receptor ◽

Type I ◽

Protein Protein Interactions ◽

Downstream Effectors ◽

Factor Type

Many GPCRs (G-protein-coupled receptors) can activate RTKs (receptor tyrosine kinases) in the absence of RTK ligands, a phenomenon called transactivation. However, the underlying molecular mechanisms remain undefined. In the present study we investigate the molecular basis of GABAB (γ-aminobutyric acid B) receptor-mediated transactivation of IGF-1R (insulin-like growth factor type I receptor) in primary neurons. We take a chemical biology approach by developing an activity-based probe targeting the GABAB receptor. This probe enables us first to lock the GABAB receptor in an inactive state and then activate it with a positive allosteric modulator, thereby permitting monitoring of the dynamic of the protein complex associated with IGF-1R transactivation. We find that activation of the GABAB receptor induces a dynamic assembly and disassembly of a protein complex, including both receptors and their downstream effectors. FAK (focal adhesion kinase), a non-RTK, plays a key role in co-ordinating this dynamic process. Importantly, this dynamic of the GABAB receptor-associated complex is critical for transactivation and transactivation-dependent neuronal survival. The present study has identified an important mechanism underlying GPCR transactivation of RTKs, which was enabled by a new chemical biology tool generally applicable for dissecting GPCR signalling.

Download Full-text

Protein-Protein Interactions in the Tetraspanin Web

Physiology ◽

10.1152/physiol.00015.2005 ◽

2005 ◽

Vol 20 (4) ◽

pp. 218-224 ◽

Cited By ~ 132

Author(s):

Shoshana Levy ◽

Tsipi Shoham

Keyword(s):

Signal Transduction ◽

Cell Proliferation ◽

Protein Interactions ◽

Membrane Microdomains ◽

Protein Protein Interactions ◽

Host Parasite Interactions ◽

Evolutionarily Conserved ◽

And Migration ◽

Host Parasite ◽

Partner Proteins

Tetraspanins are evolutionarily conserved membrane proteins that tend to associate laterally with one another and to cluster dynamically with numerous partner proteins in membrane microdomains. Consequently, members of this family are involved in the coordination of intracellular and intercellular processes, including signal transduction; cell proliferation, adhesion, and migration; cell fusion; and host-parasite interactions.

Download Full-text

Network-Based Gene Expression Biomarkers for Cold and Heat Patterns of Rheumatoid Arthritis in Traditional Chinese Medicine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/203043 ◽

2012 ◽

Vol 2012 ◽

pp. 1-17 ◽

Cited By ~ 23

Author(s):

Cheng Lu ◽

Xuyan Niu ◽

Cheng Xiao ◽

Gao Chen ◽

Qinglin Zha ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Cell Proliferation ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Protein Interactions ◽

Acid Metabolism ◽

Protein Protein Interactions ◽

Significant Gene ◽

Heat Pattern

In Traditional Chinese Medicine (TCM), patients with Rheumatoid Arthritis (RA) can be classified into two main patterns: cold-pattern and heat-pattern. This paper identified the network-based gene expression biomarkers for both cold- and heat-patterns of RA. Gene expression profilings of CD4+ T cells from cold-pattern RA patients, heat-pattern RA patients, and healthy volunteers were obtained using microarray. The differentially expressed genes and related networks were explored using DAVID, GeneSpring software, and the protein-protein interactions (PPI) method. EIF4A2, CCNT1, and IL7R, which were related to the up-regulation of cell proliferation and the Jak-STAT cascade, were significant gene biomarkers of the TCM cold pattern of RA. PRKAA1, HSPA8, and LSM6, which were related to fatty acid metabolism and the I-κB kinase/NF-κB cascade, were significant biomarkers of the TCM heat-pattern of RA. The network-based gene expression biomarkers for the TCM cold- and heat-patterns may be helpful for the further stratification of RA patients when deciding on interventions or clinical trials.

Download Full-text

Live-cell visualization of transmembrane protein oligomerization and membrane fusion using two-fragment haptoEGFP methodology

Bioscience Reports ◽

10.1042/bsr20110100 ◽

2012 ◽

Vol 32 (3) ◽

pp. 333-343 ◽

Cited By ~ 2

Author(s):

Derek J. Quinn ◽

Neil V. McFerran ◽

John Nelson ◽

W. Paul Duprex

Keyword(s):

Protein Interactions ◽

Mammalian Cells ◽

Measles Virus ◽

Fluorescent Protein ◽

Transmembrane Protein ◽

Bimolecular Fluorescence Complementation ◽

Type I ◽

Protein Oligomerization ◽

Fluorescent Signal ◽

Enveloped Virus

Protein interactions play key roles throughout all subcellular compartments. In the present paper, we report the visualization of protein interactions throughout living mammalian cells using two oligomerizing MV (measles virus) transmembrane glycoproteins, the H (haemagglutinin) and the F (fusion) glycoproteins, which mediate MV entry into permissive cells. BiFC (bimolecular fluorescence complementation) has been used to examine the dimerization of these viral glycoproteins. The H glycoprotein is a type II membrane-receptor-binding homodimeric glycoprotein and the F glycoprotein is a type I disulfide-linked membrane glycoprotein which homotrimerizes. Together they co-operate to allow the enveloped virus to enter a cell by fusing the viral and cellular membranes. We generated a pair of chimaeric H glycoproteins linked to complementary fragments of EGFP (enhanced green fluorescent protein) – haptoEGFPs – which, on association, generate fluorescence. Homodimerization of H glycoproteins specifically drives this association, leading to the generation of a fluorescent signal in the ER (endoplasmic reticulum), the Golgi and at the plasma membrane. Similarly, the generation of a pair of corresponding F glycoprotein–haptoEGFP chimaeras also produced a comparable fluorescent signal. Co-expression of H and F glycoprotein chimaeras linked to complementary haptoEGFPs led to the formation of fluorescent fusion complexes at the cell surface which retained their biological activity as evidenced by cell-to-cell fusion.

Download Full-text

In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00376.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. L1045-L1054 ◽

Cited By ~ 47

Author(s):

Jason M. Roper ◽

Dawn J. Mazzatti ◽

Richard H. Watkins ◽

William M. Maniscalco ◽

Peter C. Keng ◽

...

Keyword(s):

Epithelial Cells ◽

Transmembrane Protein ◽

Dna Integrity ◽

Alveolar Type ◽

Type I ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Cells ◽

Endogenous Expression

It is well established that hyperoxia injures and kills alveolar endothelial and type I epithelial cells of the lung. Although type II epithelial cells remain morphologically intact, it remains unclear whether they are also damaged. DNA integrity was investigated in adult mice whose type II cells were identified by their endogenous expression of pro-surfactant protein C or transgenic expression of enhanced green fluorescent protein. In mice exposed to room air, punctate perinuclear 8-oxoguanine staining was detected in ∼4% of all alveolar cells and in 30% of type II cells. After 48 or 72 h of hyperoxia, 8-oxoguanine was detected in 11% of all alveolar cells and in >60% of type II cells. 8-Oxoguanine colocalized by confocal microscopy with the mitochondrial transmembrane protein cytochrome oxidase subunit 1. Type II cells isolated from hyperoxic lungs exhibited nuclear DNA strand breaks by comet assay even though they were viable and morphologically indistinguishable from cells isolated from lungs exposed to room air. These data reveal that type II cells exposed to in vivo hyperoxia have oxidized and fragmented DNA. Because type II cells are essential for lung remodeling, our findings raise the possibility that they are proficient in DNA repair.

Download Full-text