Cdc42 promotes Bgs1 recruitment for septum synthesis and glucanase localization for cell separation during cytokinesis in fission yeast

Onwubiko, Udo N; Robinson, Julie-Rich; Mustaf, Rose Albu; Das, Maitreyi

doi:10.1101/754390

Cited by 7 publications

(21 citation statements)

References 27 publications

(36 reference statements)

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“…However, few proteins are known to regulate the localization of both classes of enzymes. Recently, Cdc42 GTPase was shown to promote recruitment of Bgs1 to the division site and be critical for proper localization of Eng1 and Agn1 (Onwubiko et al, 2020). Here we showed that Smi1 is important for division-site localization of both glucan synthases and glucanases, suggesting an interesting dual role of Smi1 in septum integrity.…”

Section: Roles Of Smi1 In Regulating Septum Integrity During Cytokinesismentioning

confidence: 55%

Involvement of Smi1 in cell wall integrity and glucan synthase Bgs4 localization during fission yeast cytokinesis

Longo

Goodyear

Zhang

et al. 2022

MBoC

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Cytokinesis is the final step of the cell-division cycle. In fungi, it relies on the coordination of constriction of an actomyosin contractile ring and construction of the septum at the division site. Glucan synthases synthesize glucans, which are the major components in fungal cell walls and division septa. It is known that Rho1 and Rho2 GTPases regulate glucan synthases Bgs1, Bgs4, and Ags1, and Sbg1 and the F-BAR protein Cdc15 play roles in Bgs1 stability and delivery to the plasma membrane. Here we characterize Smi1, an intrinsically disordered protein that interacts with Bgs4 and regulates its trafficking and localization in fission yeast. Smi1 is important for septum integrity, and its absence causes severe lysis during cytokinesis. Smi1 localizes to secretory vesicles and moves together with Bgs4 towards the division site. The concentrations of the glucan synthases Bgs1 and Bgs4 and the glucanases Agn1 and Bgl2 decrease at the division site in smi1 mutant, but Smi1 seems to be more specific to Bgs4. Mistargeting of Smi1 to mitochondria mislocalizes Bgs4, but not Bgs1. Together, our data reveal a novel regulator of glucan synthases and glucanases, Smi1, which is more important for Bgs4 trafficking, stability, and localization during cytokinesis. [Media: see text] [Media: see text]

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Section: Roles Of Smi1 In Regulating Septum Integrity During Cytokinesismentioning

confidence: 55%

Involvement of Smi1 in cell wall integrity and glucan synthase Bgs4 localization during fission yeast cytokinesis

Longo

Goodyear

Zhang

et al. 2022

MBoC

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“…Previous reports have shown that membrane trafficking events are essential for successful cytokinesis 3,6,28 . Our findings illustrate the importance of spatiotemporally regulating membrane trafficking events during cytokinesis to properly coordinate actomyosin ring constriction, membrane furrow ingression, and septum synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, after completion of ring constriction and septum maturation, the primary layer of the septum is digested by the glucanases Eng1 and Agn1 to physically separate the daughter cells, completing division [11][12][13][14][15][16] . Cdc42 activity is necessary for the delivery of the primary septum synthase Bgs1 as well as the septum digesting glucanases Eng1 and Agn1 2,3 .…”

Section: Introductionmentioning

confidence: 99%

Cdc42 GTPase activating proteins Rga4 and Rga6 coordinate septum synthesis and membrane trafficking at the division plane during cytokinesis

Campbell

Hercyk

Williams

et al. 2021

Preprint

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Fission yeast cytokinesis is driven by simultaneous septum synthesis, membrane furrowing and actomyosin ring constriction. The septum consists of a primary septum flanked by secondary septa. First, delivery of the glucan synthase Bgs1 and membrane vesicles initiate primary septum synthesis and furrowing. Next, Bgs4 is delivered for secondary septum formation. It is unclear how septum synthesis is coordinated with membrane furrowing. Cdc42 promotes delivery of Bgs1 but not Bgs4. We find that after primary septum initiation, Cdc42 inactivators Rga4 and Rga6 localize to the division site. In rga4Δrga6Δ mutants Cdc42 activity is enhanced during late cytokinesis and cells take longer to separate. Electron micrographs of the division site in these mutants exhibit malformed septum with irregular membrane structures. These mutants have a larger division plane with enhanced Bgs1 delivery but fail to enhance accumulation of Bgs4 and several exocytic proteins. Additionally, these mutants show endocytic defects at the division site. This suggests that Cdc42 regulates only specific membrane trafficking events. Our data indicate that while active Cdc42 promotes primary septum synthesis, as cytokinesis progresses Rga4 and Rga6 localize to the division site to decrease Cdc42 activity. This couples specific membrane trafficking events with septum formation to allow proper septum morphology.

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“…We have recently reported that the glucanases do not localize properly to the outer edge of the membrane barrier in a hypomorphic mutant of the small GTPase Cdc42 (Onwubiko et al, 2020). Cdc42 activity stops at the cell ends during mitosis and transitions to the division site during cytokinesis (Merla and Johnson, 2000;Rincon et al, 2007;Wei et al, 2016).…”

Section: Cdc42 Activation At Cell Ends Is Cell-cycle-dependentmentioning

confidence: 99%

“…The Rho GTPase Cdc42 is a major regulator of cell growth and polarity, and is highly conserved among eukaryotes (Etienne-Manneville, 2004;Johnson, 1999). Recently, we have shown that Cdc42 also plays a role in cytokinesis Onwubiko et al, 2020;Wei et al, 2016). Regulation of Cdc42 determines when and where polarization occurs (Das et al, 2012;Das et al, 2009;Etienne-Manneville, 2004;Howell et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Cdc42 reactivation at growth sites is regulated by local cell-cycle-dependent loss of its GAP Rga4

Rich-Robinson

Russell

Mancini

et al. 2020

Preprint

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Cells undergo polarized growth to acquire shapes that promote function. In fission yeast, polarized cell growth is driven by the Morphogenesis Orb6 (MOR) pathway and the small GTPase Cdc42. After cell division, the MOR pathway first promotes cell separation, the final step in cytokinesis, and then promotes polarized growth at the cell ends. It is unclear how the ends initiate growth after the cells separate. It is plausible that the MOR pathway activates end growth only after successful cell separation. To test this, we developed a system whereby we delay cytokinesis, while mitosis progresses, via a temporary Latrunculin A (LatA) treatment. Mitotic cells treated with LatA, when allowed to recover, initiate end growth without cell separation. We call this the PrESS phenotype - polar elongation sans cell separation. PrESS cells reactivate Cdc42 at the ends before completing cytokinesis, indicating that these are independent processes. Cell ends siphon away Cdc42, its regulators, and trafficking machinery from the cell middle, suggesting a competition between the ends and the middle. The cell middle loses this competition and fails cell separation since the requisite digestive enzymes are not properly trafficked. Our candidate screen identifies a role for Rga4, a Cdc42 inhibitor, in growth reactivation at the cell ends. Consistently, we find that the Rga4 distribution pattern along the cortex changes with the cell-cycle stage, displaying a punctate appearance mostly relegated to the cell sides during G2, and a diffuse appearance extending to the cell ends during mitosis. We hypothesize that growth at cell ends requires Rga4 removal from the ends after mitosis as well as MOR pathway activation. To test this, we constitutively activated the MOR pathway in an rga4Δ mutant. Cells constitutively activating the MOR pathway often lyse due to premature synthesis and delivery of digestive enzymes to the division site. We find that deleting rga4 from these cells rescues lysis, and recapitulates the PrESS phenotype by promoting end growth and preventing cell separation. Therefore, we propose that cell-cycle-dependent removal of Rga4 from the cell ends allows local Cdc42 reactivation and polarized growth.

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Cdc42 promotes Bgs1 recruitment for septum synthesis and glucanase localization for cell separation during cytokinesis in fission yeast

Cited by 7 publications

References 27 publications

Involvement of Smi1 in cell wall integrity and glucan synthase Bgs4 localization during fission yeast cytokinesis

Involvement of Smi1 in cell wall integrity and glucan synthase Bgs4 localization during fission yeast cytokinesis

Cdc42 GTPase activating proteins Rga4 and Rga6 coordinate septum synthesis and membrane trafficking at the division plane during cytokinesis

Cdc42 reactivation at growth sites is regulated by local cell-cycle-dependent loss of its GAP Rga4

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