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First published online 10 February 2009
doi: 10.1242/jcs.036012

Journal of Cell Science 122, 625-635 (2009)
Published by The Company of Biologists 2009
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Research Article

A signal comprising a basic cluster and an amphipathic {alpha}-helix interacts with lipids and is required for the transport of Ist2 to the yeast cortical ER

Kiran Maass1,*, Marcel André Fischer1,*, Markus Seiler2, Koen Temmerman3, Walter Nickel3 and Matthias Seedorf1,{ddagger}

1 Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany
2 European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
3 Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany

{ddagger} Author for correspondence (e-mail: m.seedorf{at}zmbh.uni-heidelberg.de)

Accepted 2 November 2008

The yeast integral membrane protein Ist2 is encoded by a bud-localised mRNA and accumulates at patch-like domains of the cell periphery, either at the cortical ER or at ER-associated domains of the plasma membrane. Transport of IST2 mRNA and local protein synthesis are not prerequisite for this localisation, indicating that Ist2 can travel through the general ER to membranes at the cell periphery. Here, we describe that the accumulation of Ist2 at the cortical ER requires a cytosolically exposed complex sorting signal that can interact with lipids at the yeast plasma membrane. Binding of the Ist2 sorting signal to lipids and rapid and efficient transport of Ist2 from perinuclear to cortical ER depend on a cluster of lysine residues, the formation of an amphipathic {alpha}-helix and a patch of hydrophobic side chains positioned at one side of the amphipathic {alpha}-helix. We suggest that a direct interaction of the Ist2 sorting signal with lipids at the plasma membrane places Ist2 at contact sites between cortical ER and plasma membrane. This provides a physical link of an integral membrane protein of the cortical ER with the plasma membrane and might allow direct transport of proteins from cortical ER to domains of the plasma membrane.

Key words: Cortical ER, Plasma membrane, Sorting signal, Lipid binding, Sec-independent trafficking


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