The Major Nuclear Envelope Targeting Domain of LAP2 Coincides with Its Lamin Binding Region but Is Distinct from Its Chromatin Interaction Domain

doi:10.1074/jbc.273.7.4213

The Major Nuclear Envelope Targeting Domain of LAP2 Coincides with Its Lamin Binding Region but Is Distinct from Its Chromatin Interaction Domain*

From the Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037

Abstract

LAP2 is an integral protein of the inner nuclear membrane which binds lamins and chromosomes and is suggested to have an important role in nuclear envelope organization. In a previous study we identified an internal 76-amino acid region of LAP2 which is required for stable targeting of the protein to the nuclear envelope. Here, we have mapped the lamin binding region of LAP2 and demonstrate that it coincides with this nuclear envelope targeting domain. In contrast, we found that the portion of LAP2 involved in binding to chromosomes resides in a separate region of the protein near its NH₂ terminus. The minimal lamin binding region of LAP2 is capable of conferring stable nuclear envelope localization when attached to the transmembrane and partial lumenal domains of a protein that shows no nuclear envelope targeting activity. This directly supports the notion that a major mechanism for localization of integral membrane proteins at the inner nuclear membrane involves binding to lamins, which would constrain diffusion through the continuous nuclear envelope/endoplasmic reticulum membrane system.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵‡ The first two authors contributed equally to this study.
↵§ Present address: Division of Biological Sciences, Graduate School of Science, Nagoya University, Nagoya Japan 464-01.
↵¶ To whom correspondence should be addressed: Dept. of Cell Biology, The Scripps Research Institute, Mail Drop IMM-10, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: 619-784-8514; Fax: 619-784-9132; E-mail: lgerace{at}scripps.edu.
↵1 The abbreviations used are: NE, nuclear envelope; ER, endoplasmic reticulum; LAP, lamina-associated protein; LBR, p58/lamin B receptor; HA, hemagglutinin; GST, glutathioneS-transferase.
↵2 C. Fritze and L. Gerace, unpublished observations.
- Received October 30, 1997.
- Revision received December 3, 1997.
The American Society for Biochemistry and Molecular Biology, Inc.