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Yeast homologue of neuronal frequenin is a regulator of phosphatidylinositol-4-OH kinase

Nature Cell Biology volume 1, pages 234–241 (1999)Cite this article

Abstract

In metazoans, certain calmodulin-related calcium-binding proteins (recoverins, neurocalcins and frequenins) are found at highest levels in excitable cells, but their physiological roles are largely uncharacterized. Here we show that Saccharomyces cerevisiae contains a frequenin homologue, Frq1, and that its target is Pik1, a phosphatidylinositol-4-OH kinase. Frq1 binds to a conserved sequence motif in Pik1 outside Pik1’s catalytic domain and stimulates its activity in vitro. N-myristoylated Frq1 may also assist in Pik1 localization.

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Figure 1: The FRQ1 gene product is a frequenin-like protein.
Figure 2: FRQ1 is an essential gene and the functional homologue of vertebrate frequenin.
Figure 3: PIK1, encoding an essential PtdIns-4-OH kinase, is a dosage suppressor of the temperature-sensitive lethality of the frq1-1ts mutation.
Figure 4: Overexpression of FRQ1 suppresses the temperature-sensitive lethality of pik1ts mutations in an allele-specific manner.
Figure 5: Frq1 associates physically with Pik1.
Figure 6: A conserved N-terminal sequence in Pik1 is both necessary and sufficient for binding of Frq1.
Figure 7: Interaction with Frq1 stimulates the catalytic activity of Pik1.
Figure 8: Optimal function of Frq1 requires its N-myristoylation.

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Acknowledgements

We thank A. Dunn and D. S. King for technical assistance; K. Matsuoka for help with PtdIns-4-OH kinase assays; J. Adamkewicz and M. Kim for purified Mot1C–His6 protein; B. Lu for frequenin cDNA and antibodies; L. Stryer for recoverin cDNA and antibodies; and S. Emr, M. Hall and D. Voelker for plasmids. This work was supported by USPHS Predoctoral Traineeships GM07232 (to K.B.H. and E.A.S.), NIH–NRSA Postdoctoral Fellowship CA73380 (to B.Q.W.), NIH Research Grant GM21841 (to J.T.), and facilities provided by the Berkeley campus Cancer Research Laboratory.

Correspondence and requests for materials should be addressed to J.T.

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  1. Elisabeth A. Schnieders

    Present address: Acacia Biosciences Inc., 4136 Lakeside Drive, Richmond, California, 94806, USA

Authors and Affiliations

  1. Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, 94720-3202, California, USA

    Kristin B. Hendricks, Bo Qing Wang, Elisabeth A. Schnieders & Jeremy Thorner

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Hendricks, K., Qing Wang, B., Schnieders, E. et al. Yeast homologue of neuronal frequenin is a regulator of phosphatidylinositol-4-OH kinase . Nat Cell Biol 1, 234–241 (1999). https://doi.org/10.1038/12058

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