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A Proteome-wide Screen for Mammalian SxIP Motif-Containing Microtubule Plus-End Tracking Proteins

Microtubule plus-end tracking proteins (+TIPs) are structurally and functionally diverse factors that accumulate at the growing microtubule plus-ends, connect them to various cellular structures, and control microtubule dynamics [1, 2]. EB1 and its homologs are +TIPs that can autonomously recognize...

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Bibliographic Details
Published in:Current biology 2012-10, Vol.22 (19), p.1800-1807
Main Authors: Jiang, Kai, Toedt, Grischa, Montenegro Gouveia, Susana, Davey, Norman E., Hua, Shasha, van der Vaart, Babet, Grigoriev, Ilya, Larsen, Jesper, Pedersen, Lotte B., Bezstarosti, Karel, Lince-Faria, Mariana, Demmers, Jeroen, Steinmetz, Michel O., Gibson, Toby J., Akhmanova, Anna
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Language:English
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Summary:Microtubule plus-end tracking proteins (+TIPs) are structurally and functionally diverse factors that accumulate at the growing microtubule plus-ends, connect them to various cellular structures, and control microtubule dynamics [1, 2]. EB1 and its homologs are +TIPs that can autonomously recognize growing microtubule ends and recruit to them a variety of other proteins. Numerous +TIPs bind to end binding (EB) proteins through natively unstructured basic and serine-rich polypeptide regions containing a core SxIP motif (serine-any amino acid-isoleucine-proline) [3]. The SxIP consensus sequence is short, and the surrounding sequences show high variability, raising the possibility that undiscovered SxIP containing +TIPs are encoded in mammalian genomes. Here, we performed a proteome-wide search for mammalian SxIP-containing +TIPs by combining biochemical and bioinformatics approaches. We have identified a set of previously uncharacterized EB partners that have the capacity to accumulate at the growing microtubule ends, including protein kinases, a small GTPase, centriole-, membrane-, and actin-associated proteins. We show that one of the newly identified +TIPs, CEP104, interacts with CP110 and CEP97 at the centriole and is required for ciliogenesis. Our study reveals the complexity of the mammalian +TIP interactome and provides a basis for investigating the molecular crosstalk between microtubule ends and other cellular structures. ► Combining proteomics with bioinformatics is an effective way of +TIP identification ► SxIP motif-containing EB-binding +TIPs are numerous in mammalian genomes ► CEP104 is an EB-binding +TIP involved in ciliogenesis ► AMER2 reveals microtubule tip-plasma membrane contacts
ISSN:0960-9822
1879-0445
DOI:10.1016/j.cub.2012.07.047