The AKAP Yu is required for olfactory long-term memory formation in Drosophila

doi:10.1073/pnas.0700439104

The AKAP Yu is required for olfactory long-term memory formation in Drosophila

*Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China;
^†JoeKai, Inc., Beijing 100084, China; and
^‡Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724

Edited by Eric R. Kandel, Columbia University, New York, NY, and approved July 13, 2007 (received for review January 17, 2007)

Abstract

Extensive neurogenetic analysis has shown that memory formation depends critically on cAMP-protein kinase A (PKA) signaling. Details of how this pathway is involved in memory formation, however, remain to be fully elucidated. From a large-scale behavioral screen in Drosophila, we identified the yu mutant to be defective in one-day memory after spaced training. The yu mutation disrupts a gene encoding an A-kinase anchoring protein (AKAP). AKAPs comprise a family of proteins, which determine the subcellular localization of PKAs and thereby critically restrict cAMP signaling within a cell. Further behavioral characterizations revealed that long-term memory (LTM) was disrupted specifically in the yu mutant, whereas learning, short-term memory and anesthesia-resistant memory all appeared normal. Another independently isolated mutation of the yu gene failed to complement the LTM defect associated with the yu mutation, and this phenotypic defect could be rescued by induced acute expression of a yu ⁺ transgene, suggesting that yu functions physiologically during memory formation. AKAP Yu is expressed preferentially in the mushroom body (MB) neuroanatomical structure, and expression of a yu ⁺ transgene to the MB, but not to other brain regions, is sufficient to rescue the LTM defect of the yu mutant. These observations lead us to conclude that proper localization of PKA by Yu AKAP in MB neurons is required for the formation of LTM.

Footnotes

^§To whom correspondence may be addressed. E-mail: zhongyi{at}cshl.edu or zhm-dbs{at}mail.tsinghua.edu.cn
Author contributions: Y.L. and Y.-S.L. contributed equally to this work; Y.L., Y.Z., and H.-M.Z. designed research; Y.L., Y.-S.L., Y.S., and C.F. performed research; T.T. and Z.X. contributed new reagents/analytic tools; Y.L., Y.-S.L., C.F., T.T., Y.Z., and H.-M.Z. analyzed data; and Y.L., Y.Z., and H.-M.Z. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700439104/DC1.
Abbreviations:

AKAP,

A-kinase anchoring protein;

ARM,

anesthesia-resistant memory;

LTM,

long-term memory;

MB,

mushroom body;

PI,

performance index;

PKA,

protein kinase A;

MTM,

middle-term memory;

RT,

room temperature;

STM,

short-term memory.