Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function

Lerit, Dorothy A.; Jordan, Holly A.; Poulton, Joanna; Fagerstrom, Carey J.; Galletta, Brian J.; Peifer, Mark; Rusan, Nasser M.

doi:10.1083/jcb.201503117

Cited by 67 publications

(120 citation statements)

References 86 publications

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“…During cell‐cycle progression, centrosomes duplicate and become fully separated by prophase along with an accompanying increase in microtubule nucleation (Tanenbaum & Medema, ). Previous work indicates PLP serves as a centrosome scaffold protein and also contributes to centrosome separation in the soma region of syncytial embryos (Lerit et al, ; Richens et al, ). A plausible hypothesis, therefore, is that defects in centrosome separation may contribute to the aberrant PB protrusion in plp mutants.…”

Section: Resultsmentioning

confidence: 97%

“…To mechanistically address how loss of plp disrupts microtubule assembly, we examined the distribution of Cnn at PB centrosomes in control versus plp GLC embryos. Cnn is a core component of a PCM scaffold required for centrosome and microtubule organization (Conduit, Brunk, et al, ; Conduit, Feng, et al, ; Lerit et al, ; Megraw, Li, Kao, & Kaufman, ; Richens et al, ). In control PBs, Cnn radiates from interphase centrosomes (Figure c, WT interphase), similar to the Cnn flares previously described in the soma (Megraw et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…The microtubule-nucleating activity of centrosomes is instructed through the pericentriolar material (PCM), a composite of numerous proteins that surrounds the central pair of centrioles (Nigg & Raff, 2009). We recently demonstrated a direct interaction between the PCM components Cnn and Pericentrin (Pcnt)-like-protein (PLP) supports the formation of a centrosome scaffold required to organize the PCM structure (Lerit et al, 2015;Richens et al, 2015). Loss of either cnn or plp results in similar embryonic defects: disorganized PCM and microtubules, centrosome spacing defects, aberrant spindle formation, and embryonic lethality (Lerit et al, 2015;Megraw, Kilaru, Turner, & Kaufman, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Drosophila pericentrin‐like protein promotes the formation of primordial germ cells

Fang

Lerit

2019

Genesis

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Summary Primordial germ cells (PGCs) are the precursors to the adult germline stem cells that are set aside early during embryogenesis and specified through the inheritance of the germ plasm, which contains the mRNAs and proteins that function as the germline fate determinants. In Drosophila melanogaster, formation of the PGCs requires the microtubule and actin cytoskeletal networks to actively segregate the germ plasm from the soma and physically construct the pole buds (PBs) that protrude from the posterior cortex. Of emerging importance is the central role of centrosomes in the coordination of microtubule dynamics and actin organization to promote PGC development. We previously identified a requirement for the centrosome protein Centrosomin (Cnn) in PGC formation. Cnn interacts directly with Pericentrin‐like protein (PLP) to form a centrosome scaffold structure required for pericentriolar material recruitment and organization. In this study, we identify a role for PLP at several discrete steps during PGC development. We find PLP functions in segregating the germ plasm from the soma by regulating microtubule organization and centrosome separation. These activities further contribute to promoting PB protrusion and facilitating the distribution of germ plasm in proliferating PGCs.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Drosophila pericentrin‐like protein promotes the formation of primordial germ cells

Fang

Lerit

2019

Genesis

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“…These maternally mutant animals do not develop beyond the first few divisions; however, zygotic mutant animals can be obtained due to maternal provisioning of centrosome-associated proteins necessary to proceed through these early divisions. Early embryos mutant for the key PCM components cnn , asl , or plp can result in aberrant mitotic spindles, centrosome separation defects, and DNA damage (Megraw et al, 1999; Vaizel-Ohayon and Schejter, 1999; Varmark et al, 2007; Lerit et al, 2015). Similarly, in C. elegans embryos, depletion of the pro-mitotic centrosome maturation factor, Air-1, results in aberrant spindles that drive polyploidy, chromatin bridges, and severe aneuploidy that collectively promote embryonic lethality (Schumacher et al, 1998).…”

Section: Centrosomes Are Vital For Efficient Spindle Assembly In Mitosismentioning

confidence: 99%

Centrosomes are multifunctional regulators of genome stability

Lerit

Poulton

2015

Chromosome Res

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The maintenance of genome stability is critical for proper cell function, and loss of this stability contributes to many human diseases and developmental disorders. Therefore, cells have evolved partially redundant mechanisms to monitor and protect the genome. One subcellular organelle implicated in the maintenance of genome stability is the centrosome, best known as the primary microtubule organizing center of most animal cells. Centrosomes serve many different roles throughout the cell cycle, and many of those roles, including mitotic spindle assembly, nucleation of the interphase microtubule array, DNA damage response, and efficient cell cycle progression, have been proposed to help maintain genome stability. As a result, the centrosome is itself a highly regulated entity. Here, we review evidence concerning the significance of the centrosome in promoting genome integrity. Recent advances permitting acute and persistent centrosome removal suggest we still have much to learn regarding the specific function and actual importance of centrosomes in different contexts, as well as how cells may compensate for centrosome dysfunction to maintain the integrity of the genome. Although many animal cells survive and proliferate in the absence of centrosomes, they do so aberrantly. Based on these and other studies, we conclude that centrosomes serve as critical, multifunctional organelles that promote genome stability.

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“…This is consistent with studies describing that Cnn forms multi-protein cytoplasmic complexes that are required for PCM formation. 29,30 After complex formation, Polo kinase binds to the Cnn bindings site at S22 (or another substrate associated with Cnn). Once bound, Polo phosphorylates Cnn at T27 (in trans, if bound to another substrate), driving the localization of Cnn-PA to the centrosome.…”

mentioning

confidence: 99%

The end of a monolith: Deconstructing the Cnn-Polo interaction

Eisman

Phelps

2016

Fly

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In Drosophila melanogaster a functional pericentriolar matrix (PCM) at mitotic centrosomes requires Centrosomin-Long Form (Cnn-LF) proteins. Moreover, tissue culture cells have shown that the centrosomal localization of both Cnn-LF and Polo kinase are co-dependent, suggesting a direct interaction. Our recent study found Cnn potentially binds to and is phosphorylated by Polo kinase at 2 residues encoded by Exon1A, the initiating exon of a subset of Cnn isoforms. These interactions are required for the centrosomal localization of Cnn-LF in syncytial embryos and a mutation of either phosphorylation site is sufficient to block localization of both mutant and wild-type Cnn when they are co-expressed. Immunoprecipitation experiments show that Cnn-LF interacts directly with mitotically activated Polo kinase and requires the 2 phosphorylation sites in Exon1A. These IP experiments also show that Cnn-LF proteins form multimers. Depending on the stoichiometry between functional and mutant peptides, heteromultimers exhibit dominant negative or positive trans-complementation (rescue) effects on mitosis. Additionally, following the completion of meiosis, Cnn-Short Form (Cnn-SF) proteins are required for polar body formation in embryos, a process previously shown to require Polo kinase. These findings, when combined with previous work, clearly demonstrate the complexity of cnn and show that a view of cnn as encoding a single peptide is too simplistic.

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Interphase centrosome organization by the PLP-Cnn scaffold is required for centrosome function

Abstract: Cnn and PLP directly interact at two defined sites to coordinate the cell cycle–dependent rearrangement and scaffolding activity of the centrosome to permit normal centrosome organization, cell division, and embryonic viability.

Cited by 67 publications

References 86 publications

Drosophila pericentrin‐like protein promotes the formation of primordial germ cells

Drosophila pericentrin‐like protein promotes the formation of primordial germ cells

Centrosomes are multifunctional regulators of genome stability

The end of a monolith: Deconstructing the Cnn-Polo interaction

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