Dissecting the sequence specific functions of alternative N-terminal isoforms of mouse bullous pemphigoid antigen 1

Exp Cell Res. 2006 Sep 10;312(15):2712-25. doi: 10.1016/j.yexcr.2006.04.025. Epub 2006 May 23.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology*
  • Chlorocebus aethiops
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / physiology*
  • Dystonin
  • Exons
  • Fluorescent Antibody Technique
  • Humans
  • Mice
  • Models, Genetic
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology*
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Transfection

Substances

  • Actins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Dst protein, mouse
  • Dystonin
  • Nerve Tissue Proteins
  • Protein Isoforms