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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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Primary sequences of mouse BPAG1 isoforms and comparison of the IFBDs. The IFBD of BPAG1-b (IFBD2; amino acids 1563–1931 of BPAG1-b) is compared with the IFBD of BPAG1-e (IFBD1; amino acids 2184–2598 of BPAG1-e). Identical amino acids are shaded in black with white letters, whereas the conserved amino acid changes are shaded in gray.
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fig2: Primary sequences of mouse BPAG1 isoforms and comparison of the IFBDs. The IFBD of BPAG1-b (IFBD2; amino acids 1563–1931 of BPAG1-b) is compared with the IFBD of BPAG1-e (IFBD1; amino acids 2184–2598 of BPAG1-e). Identical amino acids are shaded in black with white letters, whereas the conserved amino acid changes are shaded in gray.

Mentions: The composite BPAG1-b cDNA is ∼23.2 kb (GenBank/EMBL/DDBJ accession no. AF396879) and codes for an 834-kD protein (Fig. S1 B). The transcript of BPAG1-b is identical to that of BPAG1-a except that it has four additional exons in the middle of the molecule, including the ∼5-kb ORF-containing exon that was found in our genomic clone (Fig. 1 A). Part of the deduced amino acid sequence of the ∼5-kb ORF exhibits significant homology to the IFBD of BPAG1-e (Fig. 2) ; hence, we designated this domain as IFBD2 and the COOH-terminal domain of BPAG1-e/n as IFBD1. In contrast to IFBD1 which contains two repeats, IFBD2 harbors only one repeat. Aside from the IFBD2, the extra sequences of BPAG1-b do not show significant homology to other proteins. The composite cDNA of mouse BPAG1-e was ∼9.0 kb (GenBank/EMBL/DDBJ accession no. AF396877) and encoded a 302-kD protein (Fig. S1 C). The protein structure of mouse BPAG1-e is similar to its human orthologue (Sawamura et al., 1991).


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)

Primary sequences of mouse BPAG1 isoforms and comparison of the IFBDs. The IFBD of BPAG1-b (IFBD2; amino acids 1563–1931 of BPAG1-b) is compared with the IFBD of BPAG1-e (IFBD1; amino acids 2184–2598 of BPAG1-e). Identical amino acids are shaded in black with white letters, whereas the conserved amino acid changes are shaded in gray.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196450&req=5

fig2: Primary sequences of mouse BPAG1 isoforms and comparison of the IFBDs. The IFBD of BPAG1-b (IFBD2; amino acids 1563–1931 of BPAG1-b) is compared with the IFBD of BPAG1-e (IFBD1; amino acids 2184–2598 of BPAG1-e). Identical amino acids are shaded in black with white letters, whereas the conserved amino acid changes are shaded in gray.
Mentions: The composite BPAG1-b cDNA is ∼23.2 kb (GenBank/EMBL/DDBJ accession no. AF396879) and codes for an 834-kD protein (Fig. S1 B). The transcript of BPAG1-b is identical to that of BPAG1-a except that it has four additional exons in the middle of the molecule, including the ∼5-kb ORF-containing exon that was found in our genomic clone (Fig. 1 A). Part of the deduced amino acid sequence of the ∼5-kb ORF exhibits significant homology to the IFBD of BPAG1-e (Fig. 2) ; hence, we designated this domain as IFBD2 and the COOH-terminal domain of BPAG1-e/n as IFBD1. In contrast to IFBD1 which contains two repeats, IFBD2 harbors only one repeat. Aside from the IFBD2, the extra sequences of BPAG1-b do not show significant homology to other proteins. The composite cDNA of mouse BPAG1-e was ∼9.0 kb (GenBank/EMBL/DDBJ accession no. AF396877) and encoded a 302-kD protein (Fig. S1 C). The protein structure of mouse BPAG1-e is similar to its human orthologue (Sawamura et al., 1991).

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