2021
DOI: 10.1242/jcs.258897
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Condensation of pericentrin proteins in human cells illuminates phase separation in centrosome assembly

Abstract: At the onset of mitosis, centrosomes expand the pericentriolar material (PCM) to maximize their microtubule-organizing activity. This step, termed centrosome maturation, ensures proper spindle organization and faithful chromosome segregation. However, as the centrosome expands, how PCM proteins are recruited and held together without membrane enclosure remains elusive. We found that endogenously expressed pericentrin (PCNT), a conserved PCM scaffold protein, condenses into dynamic granules during late G2/early… Show more

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Cited by 39 publications
(30 citation statements)
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References 166 publications
(280 reference statements)
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“…Our work here and recent studies demonstrate that +TIP networks can behave like liquid condensates (Wu et al, 2021;Maan et al, 2021;Meier et al, 2021;Song et al, 2021). This work adds to the growing list of microtubule-related processes that are driven by LLPS and provides an exciting new paradigm for how cells can spatiotemporally control microtubule dynamics through local tubulin concentration (Zhang et al, 2015;Woodruff et al, 2017;Hernández-Vega et al, 2017;King and Petry, 2020;Jiang et al, 2021;Maan et al, 2021;Meier et al, 2021;Song et al, 2021). Interrogating the mechanical properties and composition of +TIP-droplets, as well as studying their regulation throughout the cell cycle, will be exciting avenues for future research.…”
Section: Discussionmentioning
confidence: 94%
See 1 more Smart Citation
“…Our work here and recent studies demonstrate that +TIP networks can behave like liquid condensates (Wu et al, 2021;Maan et al, 2021;Meier et al, 2021;Song et al, 2021). This work adds to the growing list of microtubule-related processes that are driven by LLPS and provides an exciting new paradigm for how cells can spatiotemporally control microtubule dynamics through local tubulin concentration (Zhang et al, 2015;Woodruff et al, 2017;Hernández-Vega et al, 2017;King and Petry, 2020;Jiang et al, 2021;Maan et al, 2021;Meier et al, 2021;Song et al, 2021). Interrogating the mechanical properties and composition of +TIP-droplets, as well as studying their regulation throughout the cell cycle, will be exciting avenues for future research.…”
Section: Discussionmentioning
confidence: 94%
“…LLPS is the process by which molecules spontaneously condensate into droplets and de-mix from their surrounding solution, resulting in the co-existence of two unique liquid phases (reviewed in Boeynaems et al, 2018;Hyman et al, 2014;Shin and Brangwynne, 2017). Recently, LLPS has been implicated in driving microtubule-related processes, including spindle assembly (Zhang et al, 2015), nucleation of acentrosomal and branched microtubules (Hernández-Vega et al, 2017;King and Petry, 2020), and centrosome maturation (Woodruff et al, 2017;Jiang et al, 2021). A key shared feature of these processes is the co-condensation of tubulin with LLPS-potent microtubule-associated proteins to catalyze biochemical reactions.…”
Section: Introductionmentioning
confidence: 99%
“…Our experimental system allowed us to examine which PCM components are capable of associating with each other and with dynein to promote microtubule nucleation and anchoring independently of centrioles. The major scaffold for interphase acentriolar PCM assembly is pericentrin, which can self-associate (Jiang et al, 2021) and form clusters that recruit CDK5RAP2 and ninein, two proteins known to bind to pericentrin (Chen et al, 2014; Delaval and Doxsey, 2010; Kim and Rhee, 2014; Lawo et al, 2012). CDK5RAP2 is important for efficient microtubule nucleation, consistent with its role as an activator of γ-TuRC (Choi et al, 2010).…”
Section: Discussionmentioning
confidence: 99%
“…Furthermore, our work provided insight into the self-assembly properties of interphase PCM. It seems that while oligomerization and clustering of pericentrin molecules is important for MTOC formation both in interphase and in mitosis, during mitotic entry, pericentrin forms condensates (Jiang et al, 2021), while in interphase, pericentrin clusters show no hallmarks of liquid droplets or condensates. Moreover, the compaction and shape of these acentriolar PCM clusters depend on dynein and microtubules.…”
Section: Discussionmentioning
confidence: 99%
“…LLPS is the process by which molecules spontaneously condense into droplets and de-mix from their surrounding solution, resulting in the co-existence of two unique liquid phases (reviewed in Boeynaems et al, 2018;Hyman et al, 2014;Shin and Brangwynne, 2017). Recently, LLPS has been implicated in driving microtubule-related processes, including spindle assembly (Zhang et al, 2015), nucleation of acentrosomal and branched microtubules (Hernández-Vega et al, 2017;King and Petry, 2020), and centrosome maturation (Woodruff et al, 2017;Jiang et al, 2021). A key shared feature of these processes is the co-condensation of tubulin with LLPS-potent microtubule-associated proteins to catalyze biochemical reactions.…”
Section: Introductionmentioning
confidence: 99%