Spatial and proteomic profiling reveals centrosome‐independent features of centriolar satellites

• Ladan Gheiratmand ^[1] ; Etienne Coyaud ^[2] ; Gagan D Gupta ^[1] ; Estelle MN Laurent ^[2] ; Monica Hasegan ^[1] ; Suzanna L Prosser ^[1] ; João Gonçalves ^[1] ; Brian Raught ^[3] ; Laurence Pelletier ^[4]
  1. [1] Mount Sinai Hospital

     Mount Sinai Hospital

     Canadá

     
  2. [2] 2 Princess Margaret Cancer Centre University Health Network Toronto ON Canada
  3. [3] 2 Princess Margaret Cancer Centre University Health Network Toronto ON Canada; 3 Department of Medical Biophysics University of Toronto Toronto ON Canada
  4. [4] 1 Lunenfeld‐Tanenbaum Research Institute Mount Sinai Hospital Toronto ON Canada; 4 Department of Molecular Genetics University of Toronto Toronto ON Canada

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 14, 2019
• Idioma: inglés
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  • Centriolar satellites are small electron‐dense granules that cluster in the vicinity of centrosomes. Satellites have been implicated in multiple critical cellular functions including centriole duplication, centrosome maturation, and ciliogenesis, but their precise composition and assembly properties have remained poorly explored. Here, we perform in vivo proximity‐dependent biotin identification (BioID) on 22 human satellite proteins, to identify 2,113 high‐confidence interactions among 660 unique polypeptides. Mining this network, we validate six additional satellite components. Analysis of the satellite interactome, combined with subdiffraction imaging, reveals the existence of multiple unique microscopically resolvable satellite populations that display distinct protein interaction profiles. We further show that loss of satellites in PCM1‐depleted cells results in a dramatic change in the satellite interaction landscape. Finally, we demonstrate that satellite composition is largely unaffected by centriole depletion or disruption of microtubules, indicating that satellite assembly is centrosome‐independent. Together, our work offers the first systematic spatial and proteomic profiling of human centriolar satellites and paves the way for future studies aimed at better understanding the biogenesis and function(s) of these enigmatic structures.