cDNA Cloning and Characterization of Lamina-associated Polypeptide 1C (LAP1C), an Integral Protein of the Inner Nuclear Membrane (*)

  1. Lori Martin,
  2. Cristina Crimaudo(§) and
  3. Larry Gerace(¶)
  1. From the (1) Departments of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037
  1. To whom correspondence should be addressed:
    The Scripps Research Institute, Dept. of Cell Biology, 10666 North Torrey Pines Rd., La Jolla, CA 92037.
    Tel.: 619-554-8514; Fax: 619-554-6253.
  • § Present address: Pharmacia Biotech Inc., Alameda, CA 94501.

Abstract

Lamina-associated polypeptides 1A-1C (LAPs1A-1C) are related integral membrane proteins of the inner nuclear membrane that bind to both A- and B-type lamins and have a putative role in the membrane attachment and assembly of the nuclear lamina. In this study, we have cloned a cDNA encoding LAP1C. The DNA sequence predicts a 506-amino acid protein of largely hydrophilic character with a single membrane-spanning region between residues 311-333. Mapping of the epitope recognized by the anti-LAP1 monoclonal antibody RL13 indicates that the hydrophilic domain containing residues 1-310 is exposed to the nucleoplasm and thus that LAP1C is a type II integral membrane protein. A second class of LAP1 cDNAs was isolated that contains two protein-coding nucleotide insertions in the LAP1C sequence. These probably encode parts of LAPs1A and/or −1B, suggesting that LAP1 isotypes arise from alternative splicing. Immunoblot analysis of mouse P19 teratocarcinoma cells and the P19MES-differentiated derivative of the latter suggest that LAP1 isotypes are differentially expressed during development, similar to members of the nuclear lamin family. Since the different LAP1 isotypes appear to bind lamins with different affinities, these changes in expression could be important for developmentally regulated alterations in nuclear structure.

Footnotes

  • * This work was supported by a grant from the National Institutes of Health (to L. G.) and an EMBO long-term postdoctoral fellowship (to C. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    The nucleotide sequence(s) reported in this paper has been submitted to the GenBank/EMBL Data Bank with accession number(s) U19614 and U20286.

  • 1 The abbreviations used are:

    NE

    nuclear envelope

    kb

    kilobase(s)

    ORF

    open reading frame

    nt

    nucleotide(s)

    PBS

    phosphate-buffered saline.

  • 2Furukawa, K., Panté, N., Aebi, U., and Gerace, L. (1995) EMBO J. 14, in press.

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