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The BPAG1 locus: Alternative splicing produces multiple isoforms with distinct cytoskeletal linker domains, including predominant isoforms in neurons and muscles.

Leung CL, Zheng M, Prater SM, Liem RK - J. Cell Biol. (2001)

Bottom Line: We have analyzed the BPAG1 locus in detail and found that it encodes different interaction domains that are combined in tissue-specific manners.BPAG1-a is composed of the ABD, the plakin domain, the SR-containing rod domain, and the MTBD.BPAG1-b is highly expressed in muscles, and has extra exons encoding a second IFBD between the plakin and SR-containing rod domains of BPAG1-a.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

ABSTRACT
Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family with cytoskeletal linker properties. Mutations in BPAG1 cause sensory neuron degeneration and skin fragility in mice. We have analyzed the BPAG1 locus in detail and found that it encodes different interaction domains that are combined in tissue-specific manners. These domains include an actin-binding domain (ABD), a plakin domain, a coiled coil (CC) rod domain, two different potential intermediate filament-binding domains (IFBDs), a spectrin repeat (SR)-containing rod domain, and a microtubule-binding domain (MTBD). There are at least three major forms of BPAG1: BPAG1-e (302 kD), BPAG1-a (615 kD), and BPAG1-b (834 kD). BPAG1-e has been described previously and consists of the plakin domain, the CC rod domain, and the first IFBD. It is the primary epidermal BPAG1 isoform, and its absence that is the likely cause of skin fragility in mutant mice. BPAG1-a is the major isoform in the nervous system and a homologue of the microtubule actin cross-linking factor, MACF. BPAG1-a is composed of the ABD, the plakin domain, the SR-containing rod domain, and the MTBD. The absence of BPAG1-a is the likely cause of sensory neurodegeneration in mutant mice. BPAG1-b is highly expressed in muscles, and has extra exons encoding a second IFBD between the plakin and SR-containing rod domains of BPAG1-a.

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Differential distribution of MACF and BPAG1-a/b. Adjacent transverse (A, B, and E–H) and sagittal (C and D) sections of embryonic-day-14.5 embryos were hybridized with probes prepared for the MTBD of BPAG1-a /b (A, C, E, and G) and MACF (B, D, F, and H). Hybridization signal of BPAG1-a was stronger than that of MACF in the DRG (short arrows, A and B) and metanephros (long arrows, A and B). Interestingly, there is a gradient of BPAG1-a/b distribution in the spinal cord with stronger signals detected on the ventral side (A). Note that BPAG1-a mRNA was expressed in the cartilage of the vertebrae, whereas MACF mRNA was expressed mostly in the mesenchymal tissues surrounding the developing vertebrae (C and D). Strong signals for BPAG1-b and MACF were found in the heart (E) and the lungs, respectively (H). Bars: (A and C) 0.5 mm; (H) 0.1 mm.
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fig5: Differential distribution of MACF and BPAG1-a/b. Adjacent transverse (A, B, and E–H) and sagittal (C and D) sections of embryonic-day-14.5 embryos were hybridized with probes prepared for the MTBD of BPAG1-a /b (A, C, E, and G) and MACF (B, D, F, and H). Hybridization signal of BPAG1-a was stronger than that of MACF in the DRG (short arrows, A and B) and metanephros (long arrows, A and B). Interestingly, there is a gradient of BPAG1-a/b distribution in the spinal cord with stronger signals detected on the ventral side (A). Note that BPAG1-a mRNA was expressed in the cartilage of the vertebrae, whereas MACF mRNA was expressed mostly in the mesenchymal tissues surrounding the developing vertebrae (C and D). Strong signals for BPAG1-b and MACF were found in the heart (E) and the lungs, respectively (H). Bars: (A and C) 0.5 mm; (H) 0.1 mm.

Mentions: We also compared the tissue distributions of MACF and BPAG1-a by in situ hybridization. Adjacent transverse sections of E14.5 embryos were hybridized with the MTBD probes from MACF and BPAG1-a (note that this BPAG1-a probe will not distinguish between BPAG1-a and BPAG1-b). The expression of BPAG1-a in the spinal cord was in a gradient with higher levels in the ventral horn, as compared with the homogenous expression pattern of MACF (Fig. 5, A and B) . Of note is the observation that BPAG1-a was expressed in much higher quantities than MACF in the DRG. In the vertebrae, BPAG1-a and/or BPAG1-b mRNAs were detected in developing bone cartilage, whereas MACF expression appeared to be more confined in the surrounding mesenchymal tissues (Fig. 5, C and D). Inside the thoracic cage, higher expression levels of BPAG1-b were detected in the heart, whereas MACF was more dominant in the lung.


The BPAG1 locus: Alternative splicing produces multiple isoforms with distinct cytoskeletal linker domains, including predominant isoforms in neurons and muscles.

Leung CL, Zheng M, Prater SM, Liem RK - J. Cell Biol. (2001)

Differential distribution of MACF and BPAG1-a/b. Adjacent transverse (A, B, and E–H) and sagittal (C and D) sections of embryonic-day-14.5 embryos were hybridized with probes prepared for the MTBD of BPAG1-a /b (A, C, E, and G) and MACF (B, D, F, and H). Hybridization signal of BPAG1-a was stronger than that of MACF in the DRG (short arrows, A and B) and metanephros (long arrows, A and B). Interestingly, there is a gradient of BPAG1-a/b distribution in the spinal cord with stronger signals detected on the ventral side (A). Note that BPAG1-a mRNA was expressed in the cartilage of the vertebrae, whereas MACF mRNA was expressed mostly in the mesenchymal tissues surrounding the developing vertebrae (C and D). Strong signals for BPAG1-b and MACF were found in the heart (E) and the lungs, respectively (H). Bars: (A and C) 0.5 mm; (H) 0.1 mm.
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fig5: Differential distribution of MACF and BPAG1-a/b. Adjacent transverse (A, B, and E–H) and sagittal (C and D) sections of embryonic-day-14.5 embryos were hybridized with probes prepared for the MTBD of BPAG1-a /b (A, C, E, and G) and MACF (B, D, F, and H). Hybridization signal of BPAG1-a was stronger than that of MACF in the DRG (short arrows, A and B) and metanephros (long arrows, A and B). Interestingly, there is a gradient of BPAG1-a/b distribution in the spinal cord with stronger signals detected on the ventral side (A). Note that BPAG1-a mRNA was expressed in the cartilage of the vertebrae, whereas MACF mRNA was expressed mostly in the mesenchymal tissues surrounding the developing vertebrae (C and D). Strong signals for BPAG1-b and MACF were found in the heart (E) and the lungs, respectively (H). Bars: (A and C) 0.5 mm; (H) 0.1 mm.
Mentions: We also compared the tissue distributions of MACF and BPAG1-a by in situ hybridization. Adjacent transverse sections of E14.5 embryos were hybridized with the MTBD probes from MACF and BPAG1-a (note that this BPAG1-a probe will not distinguish between BPAG1-a and BPAG1-b). The expression of BPAG1-a in the spinal cord was in a gradient with higher levels in the ventral horn, as compared with the homogenous expression pattern of MACF (Fig. 5, A and B) . Of note is the observation that BPAG1-a was expressed in much higher quantities than MACF in the DRG. In the vertebrae, BPAG1-a and/or BPAG1-b mRNAs were detected in developing bone cartilage, whereas MACF expression appeared to be more confined in the surrounding mesenchymal tissues (Fig. 5, C and D). Inside the thoracic cage, higher expression levels of BPAG1-b were detected in the heart, whereas MACF was more dominant in the lung.

Bottom Line: We have analyzed the BPAG1 locus in detail and found that it encodes different interaction domains that are combined in tissue-specific manners.BPAG1-a is composed of the ABD, the plakin domain, the SR-containing rod domain, and the MTBD.BPAG1-b is highly expressed in muscles, and has extra exons encoding a second IFBD between the plakin and SR-containing rod domains of BPAG1-a.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

ABSTRACT
Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family with cytoskeletal linker properties. Mutations in BPAG1 cause sensory neuron degeneration and skin fragility in mice. We have analyzed the BPAG1 locus in detail and found that it encodes different interaction domains that are combined in tissue-specific manners. These domains include an actin-binding domain (ABD), a plakin domain, a coiled coil (CC) rod domain, two different potential intermediate filament-binding domains (IFBDs), a spectrin repeat (SR)-containing rod domain, and a microtubule-binding domain (MTBD). There are at least three major forms of BPAG1: BPAG1-e (302 kD), BPAG1-a (615 kD), and BPAG1-b (834 kD). BPAG1-e has been described previously and consists of the plakin domain, the CC rod domain, and the first IFBD. It is the primary epidermal BPAG1 isoform, and its absence that is the likely cause of skin fragility in mutant mice. BPAG1-a is the major isoform in the nervous system and a homologue of the microtubule actin cross-linking factor, MACF. BPAG1-a is composed of the ABD, the plakin domain, the SR-containing rod domain, and the MTBD. The absence of BPAG1-a is the likely cause of sensory neurodegeneration in mutant mice. BPAG1-b is highly expressed in muscles, and has extra exons encoding a second IFBD between the plakin and SR-containing rod domains of BPAG1-a.

Show MeSH
Related in: MedlinePlus