The Anaphase-Promoting Complex and Separin Are Required for Embryonic Anterior-Posterior Axis Formation

Rappleye, Chad A.; Tagawa, Akiko; Lyczak, Rebecca; Bowerman, Bruce; Aroian, Raffi V.

doi:10.1016/s1534-5807(02)00114-4

Cited by 80 publications

(90 citation statements)

References 41 publications

(6 reference statements)

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“…In all nmy-2(RNAi) embryos (n=8), we also detected GFP:PAR-2 in foci around the pronuclei or spindle, as was reported previously for mutants that fail to polarize normally (Rappleye et al, 2002). In four out of eight time-lapse analyses, GFP:PAR-2 appeared to shuttle from the cortex to the nearest pronucleus or centrosome.…”

Section: Polarization Of the Zygote Involves Two Distinct Phasessupporting

confidence: 84%

Polarization of theC. eleganszygote proceeds via distinct establishment and maintenance phases

et al. 2003

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Polarization of the C. elegans zygote along the anteriorposterior axis depends on cortically enriched (PAR) and cytoplasmic (MEX-5/6) proteins, which function together to localize determinants (e.g. PIE-1) in response to a polarizing cue associated with the sperm asters. Using timelapse microscopy and GFP fusions, we have analyzed the localization dynamics of PAR-2, PAR-6, MEX-5, MEX-6 and PIE-1 in wild-type and mutant embryos. These studies reveal that polarization involves two genetically and temporally distinct phases.

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Section: Polarization Of the Zygote Involves Two Distinct Phasessupporting

confidence: 84%

Polarization of theC. eleganszygote proceeds via distinct establishment and maintenance phases

et al. 2003

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“…13 and 16). The APC/C is involved with the control of axon growth and brain patterning (17), regulates synaptic size and activity in Caenorhabditis elegans and Drosophila (18,19), and excludes Par-3 from the posterior cortex of the C. elegans embryo to establish its anterior-posterior axis (20). The APC/C is needed to asymmetrically localize Miranda and its cargo proteins Staufen, Prospero, and Brat during Drosophila neuroblast division, indicating a role for the APC/C in PCP (21).…”

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confidence: 99%

Regulation of ciliary polarity by the APC/C

Ganner

Lienkamp

Schäfer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Planar cell polarity signaling controls a variety of polarized cell behaviors. In multiciliated Xenopus epidermal cells, recruitment of Dishevelled (Dvl) to the basal body and its localization to the center of the ciliary rootlet are required to correctly position the motile cilia. We now report that the anaphase-promoting complex (APC/C) recognizes a D-box motif of Dvl and ubiquitylates Dvl on a highly conserved lysine residue. Inhibition of APC/C function by knockdown of the ANAPC2 subunit disrupts the polarity of motile cilia and alters the directionality of the fluid movement along the epidermis of the Xenopus embryo. Our results suggest that the APC/C activity enables cilia to correctly polarize in Xenopus epidermal cells.cilium ͉ Dishevelled ͉ planar cell polarity ͉ polycystic kidney disease ͉ ANAPC2

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“…In fission yeast, separase binds to the mitotic spindle and has been implicated in spindle pole body morphology and positioning (10 -12). In nematode worms separase is required for correct centrosome positioning during the first asymmetric mitotic division (13) as well as for formation of an intact eggshell of the one-cell embryo (14). One way in which separase could contribute to multiple processes is that target proteins other than cohesin exist and that cleavage of several proteins during mitosis coordinates these events.…”

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confidence: 99%

Studies on Substrate Recognition by the Budding Yeast Separase

Sullivan

Hornig

Porstmann

et al. 2004

Journal of Biological Chemistry

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Sister chromatid cohesion is resolved at anaphase onset when separase, a site-specific protease, cleaves the Scc1 subunit of the chromosomal cohesin complex that is responsible for holding sister chromatids together. This mechanism to initiate anaphase is conserved in eukaryotes from budding yeast to man. Budding yeast separase recognizes and cleaves two conserved peptide motifs within Scc1. In addition, separase cleaves a similar motif in the kinetochore and spindle protein Slk19. Separase may cleave further substrate proteins to orchestrate multiple cellular events that take place during anaphase. To investigate substrate recognition by budding yeast separase we analyzed the sequence requirements at one of the Scc1 cleavage site motifs by systematic mutagenesis. We derived a cleavage site consensus motif (not(FKRWY))(ACFHILMPVWY)(DE)X(AGSV)R/X. This motif is found in 1,139 of 5,889 predicted yeast proteins. We analyzed 28 candidate proteins containing this motif as well as 35 proteins that contain a core (DE)XXR motif. We could so far not confirm new separase substrates, but we have uncovered other forms of mitotic regulation of some of the proteins. We studied whether determinants other than the cleavage site motif mediate separase-substrate interaction. When the separase active site was occupied with a peptide inhibitor covering the cleavage site motif, separase still efficiently interacted with its substrate Scc1. This suggests that separase recognizes both a cleavage site consensus sequence as well as features outside the cleavage site.The segregation of sister chromatids to daughter cells during mitosis requires a complex series of cellular events to be performed faithfully, which has been studied in some detail in the budding yeast Saccharomyces cerevisiae (1). One of the key events is activation of a site-specific protease, separase, which triggers the resolution of sister chromatid cohesion at anaphase onset. Sister chromatids are kept aligned in metaphase by a protein complex, cohesin, which counteracts the pulling force of the mitotic spindle. Cohesion is lost abruptly at anaphase onset when separase cleaves the Scc1 subunit of the cohesin complex. During meiosis Scc1 in cohesin is replaced by a related subunit, Rec8, which is cleaved by separase during the two subsequent rounds of meiotic chromosome segregation. Premature loss of cohesion leads to chromosome missegregation, thus cohesin cleavage by separase is kept under tight cellular control (2).Separase is required for processes in addition to sister chromatid separation. These include anaphase spindle stabilization and the coupling of anaphase to mitotic exit during budding yeast mitosis (3-8) as well as the coordination of the chromosome segregation and spindle cycles during meiosis (9). In fission yeast, separase binds to the mitotic spindle and has been implicated in spindle pole body morphology and positioning (10 -12). In nematode worms separase is required for correct centrosome positioning during the first asymmetric mitotic division (13)...

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The Anaphase-Promoting Complex and Separin Are Required for Embryonic Anterior-Posterior Axis Formation

Cited by 80 publications

References 41 publications

Polarization of theC. eleganszygote proceeds via distinct establishment and maintenance phases

Polarization of theC. eleganszygote proceeds via distinct establishment and maintenance phases

Regulation of ciliary polarity by the APC/C

Studies on Substrate Recognition by the Budding Yeast Separase

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