Bullous pemphigoid antigen (BPAG1): cDNA cloning and mapping of the gene to the short arm of human chromosome 6

Sawamura, Daisuke; Nomura, Kazuo; Sugita, Yasuyuki; Matteï, Marie‐Geneviève; Chu, Mon‐Li; Knowlton, Robert G.; Uitto, Jouni

doi:10.1016/0888-7543(90)90261-r

Cited by 86 publications

(27 citation statements)

References 21 publications

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“…Furthermore, we analyzed a cDNA clone KIAA0728 in the HUGE data base of Kazusa DNA Research Institute, which consists of a spectrin repeat domain, two calcium binding EF-hand motifs, and a GAS2 domain. GenBank TM accession number KIAA0728 is very similar to the COOH-terminal region of MACF and maps on the same chromosome 6 as BPAG1 (26), whereas MACF maps on chromosome 1 (16). Considering these facts, we designed several primers that bind to BPAG1e, spectrin repeat region of GenBank TM accession number AL096710 or KIAA0728, and performed RT-PCR with total RNA of DJM-1 cells.…”

Section: Novel Alternative Splicing Variants Detected By Rt-pcrmentioning

confidence: 99%

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Novel Alternative Splicings of BPAG1 (Bullous Pemphigoid Antigen 1) Including the Domain Structure Closely Related to MACF (Microtubule Actin Cross-linking Factor)

Okumura

Yamakawa

Ohara

et al. 2002

Journal of Biological Chemistry

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BPAG1 (bullous pemphigoid antigen 1) was originally identified as a 230-kDa hemidesmosomal protein and belongs to the plakin family, because it consists of a plakin domain, a coiled-coil rod domain and a COOHterminal intermediate filament binding domain. To date, alternatively spliced products of BPAG1, BPAG1e, and BPAG1n are known. BPAG1e is expressed in epithelial tissues and localized to hemidesmosomes, on the other hand, BPAG1n is expressed in neural tissues and muscles and has an actin binding domain at the NH 2 -terminal of BPAG1e. BPAG1 is also known as a gene responsible for Dystonia musculorum (dt) neurodegeneration syndrome of the mouse. Another plakin family protein MACF (microtubule actin cross-linking factor) has also an actin binding domain and the plakin domain at the NH 2 -terminal. However, in contrast to its high homology with BPAG1 at the NH 2 -terminal, the COOHterminal structure of MACF, including a microtubule binding domain, resembles dystrophin rather than plakins. Here, we investigated RNAs and proteins expressed from the BPAG1 locus and suggest novel alternative splicing variants, which include one consisting of the COOH-terminal domain structure homologous to MACF. The results indicate that BPAG1 has three kinds of cytoskeletal binding domains and seems to play an important role in linking the different types of cytoskeletons. BPAG11 and BPAG2 are the autoantigens of bullous pemphigoid (BP), an autoimmune subepidermal skin blistering disease (1). Both are components of hemidesmosomes, and BPAG1 is a 230-kDa cytoplasmic protein and anchors keratin-containing intermediate filaments (IFs) to the inner plaque of hemidesmosomes (1-3). BPAG2 is a 180-kDa transmembrane protein with interrupted collagen domains in its extracellular part (1-3). BPAG1 belongs to the plakin family, including plectin, desmoplakin, envoplakin, and periplakin, which associate with IFs in various tissues (4, 5). Plakins have a common structure consisting of an amino (NH 2 )-terminal plakin domain, a central coiled-coil domain, and a carboxyl (COOH)-terminal domain containing the IF binding domain (4, 5). In addition, BPAG1 and plectin give rise to alternative splicing variants, which have an actin binding domain (ABD) at the NH 2 terminus (6 -11). BPAG1 with ABD expressed in nervous tissues and muscles are distinguished as BPAG1n from BPAG1e that has no ABD and localizes to the hemidesmosome in the epithelial tissue (11-13). Consistent with the expression and localization, BPAG1-deficient mice show skin blistering and neurodegeneration (12). Also, the mouse mutant, Dystonia musculorum (dt), which shows neurodegeneration but normal skin, is known to result from loss of BPAG1n but normal expression of BPAG1e (12).Mammalian protein MACF (microtubule actin cross-linking factor) and Drosophila protein Kakapo are classified as members of the plakin family (13-15). Human MACF was also reported as ABP620 or trabeculin-␣ (16, 17). They are a novel type of plakin proteins, because their COOH-terminal structures containing micr...

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Section: Novel Alternative Splicing Variants Detected By Rt-pcrmentioning

confidence: 99%

“…Variant Expected from the Genomic Sequences-Human BPAG1 is encoded at the chromosomal locus 6p11-12 (26), and the genomic sequence of this region is registered in the GenBank TM data base (GenBank TM accession number AL096710, Fig. 1A).…”

Section: Novel Alternative Splicing Variants Detected By Rt-pcrmentioning

confidence: 99%

Novel Alternative Splicings of BPAG1 (Bullous Pemphigoid Antigen 1) Including the Domain Structure Closely Related to MACF (Microtubule Actin Cross-linking Factor)

Okumura

Yamakawa

Ohara

et al. 2002

Journal of Biological Chemistry

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“…The BP230 antigen is restricted to the cytoplasmic plaque of the hemidesmosome and appears to interact directly with the intermediate filament network (10,11). The BP180 antigen is a type II transmembrane protein with an aminoterminal endodomain and an extended carboxyterminal ectodomain that spans the lamina lucida, projecting into the lamina densa of the BMZ (12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Role of different pathways of the complement cascade in experimental bullous pemphigoid

Nelson¹,

Zhao²,

Schroeder³

et al. 2006

J. Clin. Invest.

101

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Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies directed against the hemidesmosomal proteins BP180 and BP230 and inflammation. Passive transfer of antibodies to the murine BP180 (mBP180) induces a skin disease that closely resembles human BP. In the present study, we defined the roles of the different complement activation pathways in this model system. Mice deficient in the alternative pathway component factor B (Fb) and injected with pathogenic anti-mBP180 IgG developed delayed and less intense subepidermal blisters. Mice deficient in the classical pathway component complement component 4 (C4) and WT mice pretreated with neutralizing antibody against the first component of the classical pathway, C1q, were resistant to experimental BP. These mice exhibited a significantly reduced level of mast cell degranulation and polymorphonuclear neutrophil (PMN) infiltration in the skin. Intradermal administration of compound 48/80, a mast cell degranulating agent, restored BP disease in C4 -/-mice. Furthermore, C4 -/-mice became susceptible to experimental BP after local injection of PMN chemoattractant IL-8 or local reconstitution with PMNs. These findings provide the first direct evidence to our knowledge that complement activation via the classical and alternative pathways is crucial in subepidermal blister formation in experimental BP. IntroductionBullous pemphigoid (BP) is a subepidermal blistering skin disorder of the elderly (1). Lesional skin of BP patients is characterized by a detachment of the basal keratinocytes of the epidermis from the dermis, resulting in tense, fluid-filled vesicles. Similar skin lesions were noted in herpes gestationis (HG), a nonviral disease of pregnancy (2). Immunofluorescence (IF) studies demonstrated that these patients exhibit circulating and tissue-bound autoantibodies directed against antigens of the basement membrane zone (BMZ) (3-8).BP and HG autoantibodies recognize 2 antigens, BP230 and BP180, that are localized in the hemidesmosome, the main epidermal structure involved in dermal-epidermal adhesion (4-6, 9). The BP230 antigen is restricted to the cytoplasmic plaque of the hemidesmosome and appears to interact directly with the intermediate filament network (10, 11). The BP180 antigen is a type II transmembrane protein with an aminoterminal endodomain and an extended carboxyterminal ectodomain that spans the lamina lucida, projecting into the lamina densa of the BMZ (12-16). The ectodomain of human BP180 contains a series of 15 interrupted collagen domains (complement components 1-15 [C1-C15]) with the typical Gly-X-Y repeat (14). It has recently been shown that the BP180 extracellular domain forms a collagen triple helix (17, 18). The extracellular noncollagenous stretches are designated NC1 (located at the carboxyl terminus) through NC16A (adjacent to the membrane-spanning domain). The NC16A domain of human BP180 harbors major extracellular antigenic sites recognized by BP and HG sera (19,20).Complement can be activated...

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“…Work in mammalian intestinal epithelial cells, 3D cultures and short-term epithelial Box 1. Isoforms originating from splicing Differential splicing of the mammalian BPAG1 gene gives rise to several proteins, with the first BPAG1 isoforms reported being BPAG1e and BPAG1n (Li et al, 1992;Sawamura et al, 1990). Additional BPAG1e isoforms, including BPAG1eA, BPAG1eS and BPAG1eB, are found in muscle (Okumura et al, 2002).…”

Section: The Various Binding Partners Of Spektraplakinsmentioning

confidence: 99%

Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles

Zhang

Yue

2017

Journal of Cell Science

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The different cytoskeletal networks in a cell are responsible for many fundamental cellular processes. Current studies have shown that spectraplakins, cytoskeletal crosslinkers that combine features of both the spectrin and plakin families of crosslinkers, have a critical role in integrating these different cytoskeletal networks. Spectraplakin genes give rise to a variety of isoforms that have distinct functions. Importantly, all spectraplakin isoforms are uniquely able to associate with all three elements of the cytoskeleton, namely, F-actin, microtubules and intermediate filaments. In this Review, we will highlight recent studies that have unraveled their function in a wide range of different processes, from regulating cell adhesion in skin keratinocytes to neuronal cell migration. Taken together, this work has revealed a diverse and indispensable role for orchestrating the function of different cytoskeletal elements in vivo.

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Bullous pemphigoid antigen (BPAG1): cDNA cloning and mapping of the gene to the short arm of human chromosome 6

Cited by 86 publications

References 21 publications

Novel Alternative Splicings of BPAG1 (Bullous Pemphigoid Antigen 1) Including the Domain Structure Closely Related to MACF (Microtubule Actin Cross-linking Factor)

Novel Alternative Splicings of BPAG1 (Bullous Pemphigoid Antigen 1) Including the Domain Structure Closely Related to MACF (Microtubule Actin Cross-linking Factor)

Role of different pathways of the complement cascade in experimental bullous pemphigoid

Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles

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