title: A Proteome-wide screen for mammalian SxIP motif-containing microtubule plus-end tracking proteins.
abstract: 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.
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.forename: Grischa
authors.initials: G
authors.lastname: Toedt
authors.forename: Susana
authors.initials: S
authors.lastname: Montenegro Gouveia
authors.forename: Norman E
authors.initials: NE
authors.lastname: Davey
authors.forename: Shasha
authors.initials: S
authors.lastname: Hua
authors.forename: Babet
authors.initials: B
authors.lastname: van der Vaart
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Jesper
authors.initials: J
authors.lastname: Larsen
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Pedersen
authors.forename: Karel
authors.initials: K
authors.lastname: Bezstarosti
authors.forename: Mariana
authors.initials: M
authors.lastname: Lince-Faria
authors.forename: Jeroen
authors.initials: J
authors.lastname: Demmers
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Gibson
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008322:Mammals; D013058:Mass Spectrometry; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism*; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction
chemical_list: D000199:Actins; C474898:CNTRL protein, human; D018797:Cell Cycle Proteins; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D020543:Proteome