Sequential and Distinct Roles of the Cadherin Domain-containing Protein Axl2p in Cell Polarization in Yeast Cell Cycle

Xiang-Dong Gao,* ${dagger}$ Lauren M. Sperber,* Steven A. Kane,* Zongtian Tong,* Amy Hin Yan Tong, ${ddagger}$ Charles Boone, ${ddagger}$ and Erfei Bi*

^*Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058; Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada

Monitoring Editor: Tim Stearns

Polarization of cell growth alonga defined axis is essential for the generation of cell and tissuepolarity. In the budding yeast S. cerevisiae, Axl2p plays anessential role in polarity-axis determination or more specifically,axial budding in MATa or ${alpha}$ cells. Axl2p is a type I membraneglycoprotein containing four cadherin-like motifs in its extracellulardomain. However, it is not known when and how Axl2p functionstogether with other components of the axial landmark, such asBud3p and Bud4p, to direct axial budding. Here, we show thatthe recruitment of Axl2p to the bud neck after S/G2 phase ofthe cell cycle depends on Bud3p and Bud4p. This recruitmentis mediated via an interaction between Bud4p and the centralregion of the Axl2p cytoplasmic tail. This region of Axl2p,together with its N-terminal region and its transmembrane domain,is sufficient for axial budding. In addition, our work demonstratesa previously unappreciated role for Axl2p. Axl2p interacts withCdc42p and other polarity-establishment proteins, and regulatesseptin organization in late G1 independently of its role inpolarity-axis determination. Together, these results suggestthat Axl2p plays sequential and distinct roles in the regulationof cellular morphogenesis in yeast cell cycle.

Present address: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.

Address correspondence to: Erfei Bi (ebi{at}mail.med.upenn.edu)