Dissecting the sequence specific functions of alternative N-terminal isoforms of mouse bullous pemphigoid antigen 1.
Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family of proteins that is involved in cross-linking the cytoskeletal elements and attaching them to cell junctions. BPAG1 null mice develop severe degeneration of sensory neurons that was attributed in part due to the absence of a splice variant called BPAG1a that harbors an actin-binding domain at the N-terminus. Additional alternative splicing also results in BPAG1a isoforms with different first exons, leading to three additional types of BPAG1a called isoforms 1, 2 and 3 (or BPAG1a1, BPAG1a2, and BPAG1a3). These unique N-terminal extensions of the BPAG1a isoforms are of variable length. In this study, we characterized these N-terminal isoforms and evaluated the influence of these unique N-terminal sequences to the actin-binding properties. The unique N-terminal region of isoform 1 is very short and was not expected to affect the property of the ABD that followed it. In contrast, transfection studies and mutagenesis analyses signified that the N-terminal sequences of isoform 2 had the ability to bundle actin filaments and the N-terminal region that contained isoform 3 showed cortical localization. Isoforms 1, 2 and 3 also displayed differential tissue expression profiles. Taken together, these data suggested that the unique N-terminal regions of these isoforms have different roles that may be tailored to meet tissue specific functions.
Jefferson
Julius J
JJ
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Leung
Conrad L
CL
Liem
Ronald K H
RK
D000199:Actins / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000502:physiology*; D000071821:Dystonin; D005091:Exons; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014162:Transfection
D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C095667:Dst protein, mouse; D000071821:Dystonin; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms