Intracellular Trafficking Pathway of Yeast Long-chain Base Kinase Lcb4, from Its Synthesis to Its Degradation*
- Soichiro Iwaki‡,1,
- Takamitsu Sano‡,1,
- Tomoko Takagi§,
- Masako Osumi¶∥,
- Akio Kihara‡,2 and
- Yasuyuki Igarashi‡,**
- ‡Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, the §Division of Biology, Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, the ¶Laboratory of Electron Microscopy/Open Research Center, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681, the ∥Integrated Imaging Research Support, Villa Royal Hirakawa, 1-7-5, Hirakawacho, Chiyoda-ku Tokyo 102-0093, and the **Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Sciences, Hokkaido University, Kita 21-jo, Nishi 11-choume, Kita-ku, Sapporo 001-0021, Japan
- ↵2 To whom correspondence should be addressed. Tel.: 81-11-706-3971; Fax: 81-11-706-4986; E-mail: kihara{at}pharm.hokudai.ac.jp.
Abstract
Sphingoid long-chain base 1-phosphates act as bioactive lipid molecules in eukaryotic cells. In budding yeast, long-chain base 1-phosphates are synthesized mainly by the long-chain base kinase Lcb4. We recently reported that, soon after yeast cells enter into the stationary phase, Lcb4 is rapidly degraded by being delivered to the vacuole in a palmitoylation- and phosphorylation-dependent manner. In this study, we investigated the complete trafficking pathway of Lcb4, from its synthesis to its degradation. After membrane anchoring by palmitoylation at the Golgi apparatus, Lcb4 is delivered to the plasma membrane (PM) through the late Sec pathway and then to the endoplasmic reticulum (ER). The yeast ER consists of a cortical network juxtaposed to the PM (cortical ER) with tubular connections to the nuclear envelope (nuclear ER). Remarkably, the localization of Lcb4 is restricted to the cortical ER. As the cells reach the stationary phase, G1 cell cycle arrest initiates Lcb4 degradation and its delivery to the vacuole via the Golgi apparatus. The protein transport pathway from the PM to the ER found in this study has not been previously reported. We speculate that this novel pathway is mediated by the PM-ER contact.
- Received February 23, 2007.
- Revision received July 19, 2007.
- The American Society for Biochemistry and Molecular Biology, Inc.
