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J. Biol. Chem., Vol. 283, Issue 17, 11743-11751, April 25, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/17/11743    most recent M710494200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Ma, Y. Articles by Taylor, S. S. PubMed PubMed Citation Articles by Ma, Y. Articles by Taylor, S. S. Social Bookmarking                      What's this?

A Molecular Switch for Targeting between Endoplasmic Reticulum (ER) and Mitochondria

CONVERSION OF A MITOCHONDRIA-TARGETING ELEMENT INTO AN ER-TARGETING SIGNAL IN DAKAP1^*

From the Howard Hughes Medical Institute and the Department of Chemistry and Biochemistry, and Department of Pharmacology, University of California, San Diego, La Jolla, California 92093

DAKAP1 (AKAP121, S-AKAP84), a dual specificity PKA scaffold protein, exists in several forms designated as a, b, c, and d. Whether DAKAP1 targets to endoplasmic reticulum (ER) or mitochondria depends on the presence of the N-terminal 33 amino acids (N1), and these N-terminal variants are generated by either alternative splicing and/or differential initiation of translation. The mitochondrial targeting motif, which is localized between residues 49 and 63, is comprised of a hydrophobic helix followed by positive charges ( Ma, Y., and Taylor, S. (2002) J. Biol. Chem. 277, 27328-27336[Abstract/Free Full Text] ). DAKAP1 is located on the cytosolic surface of mitochondria outer membrane and both smooth and rough ER membrane. A single residue, Asp³¹, within the first 33 residues of DAKAP1b is required for ER targeting. Asp³¹, which functions as a separate motif from the mitochondrial targeting signal, converts the mitochondrial-targeting signal into a bipartite ER-targeting signal, without destroying the mitochondria-targeting signal. Therefore DAKAP1 possesses a single targeting element capable of targeting to both mitochondria and ER, with the ER signal overlapping the mitochondria signal. The specificity of ER or mitochondria targeting is determined and switched by the availability of the negatively charged residue, Asp³¹.

Received for publication, December 26, 2007 , and in revised form, February 14, 2008.

^* This work was partially supported by National Institutes of Health Grant DK54441 (to S. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains a supplemental figure.

¹ To whom correspondence should be addressed: Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, and Department of Pharmacology, University of California, San Diego, 9500 Gilman Dr., MC 0654, La Jolla, CA 92093. Tel.: 858-534-3677; Fax: 858-534-8193; E-mail: staylor{at}ucsd.edu.

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