title: Selective chemical crosslinking reveals a Cep57-Cep63-Cep152 centrosomal complex.
abstract: The centrosome functions as the main microtubule-organizing center of animal cells and is crucial for several fundamental cellular processes. Abnormalities in centrosome number and composition correlate with tumor progression and other diseases. Although proteomic studies have identified many centrosomal proteins, their interactions are incompletely characterized. The lack of information on the precise localization and interaction partners for many centrosomal proteins precludes comprehensive understanding of centrosome biology. Here, we utilize a combination of selective chemical crosslinking and superresolution microscopy to reveal novel functional interactions among a set of 31 centrosomal proteins. We reveal that Cep57, Cep63, and Cep152 are parts of a ring-like complex localizing around the proximal end of centrioles. Furthermore, we identify that STIL, together with HsSAS-6, resides at the proximal end of the procentriole, where the cartwheel is located. Our studies also reveal that the known interactors Cep152 and Plk4 reside in two separable structures, suggesting that the kinase Plk4 contacts its substrate Cep152 only transiently, at the centrosome or within the cytoplasm. Our findings provide novel insights into protein interactions critical for centrosome biology and establish a toolbox for future studies of centrosomal proteins.
authors: Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
authors: Gražvydas
authors: G
authors: Lukinavičius
authors: Darja
authors: D
authors: Lavogina
authors: Meritxell
authors: M
authors: Orpinell
authors: Keitaro
authors: K
authors: Umezawa
authors: Luc
authors: L
authors: Reymond
authors: Nathalie
authors: N
authors: Garin
authors: Pierre
authors: P
authors: Gönczy
authors: Kai
authors: K
authors: Johnsson
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002502:Centrioles / Q000378:metabolism*; D003432:Cross-Linking Reagents; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*
chemical_list: C551028:CEP152 protein, human; C474610:CEP57 protein, human; C508298:CEP63 protein, human; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins