The CYK-4 GAP domain regulates cortical targeting of centralspindlin to promote contractile ring assembly and facilitate ring dissolution.
| Autor: | Schlientz AJ; Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA., Lee KY; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA., Sebastián Gómez-Cavazos J; Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA., Lara-González P; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA.; Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA., Desai A; Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA., Oegema K; Department of Cell & Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.; Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 30. Date of Electronic Publication: 2024 Oct 30. |
| DOI: | 10.1101/2024.10.29.620943 |
| Abstrakt: | During cytokinesis, an equatorial contractile ring partitions the cell contents. Contractile ring assembly requires an equatorial zone of active GTP-bound RhoA generated by the guanine nucleotide exchange factor ECT2 1,2 . ECT2 is activated by centralspindlin, a complex composed of two molecules each of kinesin-6 and CYK4. During anaphase, Centralspindlin is activated at the central spindle between the separating chromosomes and diffuses to the plasma membrane, where it engages with ECT2 via its N-terminal half 3,4 . The C-terminal half of CYK4 contains a lipid-binding C1 domain that contributes to plasma membrane targeting 5 and a GTPase-activating protein (GAP) domain that has an interaction surface for a Rho family GTPase, whose functions have remained unclear 1,3,4,6,7 . Here, using the one-cell stage C. elegans embryo as a model, we show that RhoA and the Rho-binding interface of the CYK4 GAP domain drive the recruitment of centralspindlin to the equatorial cortex. By contrast, a point mutant that selectively disrupts GAP activity does not prevent cortical centralspindlin recruitment but instead substantially delays dissipation of centralspindlin from the cortex. These findings suggest that positive feedback, in which centralspindlin recruitment promotes the generation of active RhoA and active RhoA drives centralspindlin recruitment, is central to the rapid assembly of the contractile ring within a narrow time window. They also indicate that the CYK4 GAP catalytic activity contributes to release of centralspindlin from the cortex, potentially to ensure timely dissolution of the contractile ring. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests. |
| Databáze: | MEDLINE |
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