Cell
Volume 138, Issue 2, 23 July 2009, Pages 366-376
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Article
An EB1-Binding Motif Acts as a Microtubule Tip Localization Signal

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Summary

Microtubules are filamentous polymers essential for cell viability. Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, migration, and morphogenesis. EB1 and its homologs are highly conserved proteins that play an important role in the targeting of +TIPs to microtubule ends, but the underlying molecular mechanism remains elusive. By using live cell experiments and in vitro reconstitution assays, we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is used by numerous +TIPs, including the tumor suppressor APC, the transmembrane protein STIM1, and the kinesin MCAK, for localization to microtubule tips in an EB1-dependent manner. Structural and biochemical data reveal the molecular basis of the EB1-SxIP interaction and explain its negative regulation by phosphorylation. Our findings establish a general “microtubule tip localization signal” (MtLS) and delineate a unifying mechanism for this subcellular protein targeting process.

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6

These authors contributed equally to this work

7

Present address: Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4002 Basel, Switzerland

8

Present address: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India

9

Present address: Roche Diagnostics GmbH, 68305 Mannheim, Germany