Abstract
Cells couple growth with division and regulate size in response to nutrient availability. In rod-shaped fission yeast, cell-size control occurs at mitotic commitment. An important regulator is the DYRK-family kinase Pom1, which forms gradients from cell poles and inhibits the mitotic activator Cdr2, itself localized at the medial cortex. Where and when Pom1 modulates Cdr2 activity is unclear as Pom1 medial cortical levels remain constant during cell elongation. Here we show that Pom1 re-localizes to cell sides upon environmental glucose limitation, where it strongly delays mitosis. This re-localization is caused by severe microtubule destabilization upon glucose starvation, with microtubules undergoing catastrophe and depositing the Pom1 gradient nucleator Tea4 at cell sides. Microtubule destabilization requires PKA/Pka1 activity, which negatively regulates the microtubule rescue factor CLASP/Cls1/Peg1, reducing CLASP's ability to stabilize microtubules. Thus, PKA signalling tunes CLASP's activity to promote Pom1 cell side localization and buffer cell size upon glucose starvation.
Highlights
Cells couple growth with division and regulate size in response to nutrient availability
In rod-shaped fission yeast cells, size control occurs at mitotic commitment
Microtubules form antiparallel bundles nucleated from the nuclear envelope with dynamic plus-ends that grow towards cell poles[27]
Summary
Cells couple growth with division and regulate size in response to nutrient availability. Pom[1], which forms concentration gradients from cell poles, restricts Cdr[2] localization to the cell middle[14,15] and phosphorylates Cdr[2] to inhibit its activation by the Ca2 þ /calmodulin-dependent protein kinase kinase (CaMKK) Ssp[1] and delay mitotic commitment[14,16]. Microtubule plus-end dynamics—growth, shrinkage, catastrophe and rescue—are regulated by a host of microtubule-associated proteins (MAPs) These include the þ TIP complex Mal3/EB1-Tip1/CLIP-170-Tea2/kinesin, the Alp14/XMAP215 polymerase and the Klp5–6/kinesin-8 (refs 28–33), which promote microtubule sliding along cell sides and restrict catastrophe events to cell poles for local Tea[4] release. These findings lead us to uncover a novel PKA-dependent regulation of microtubule dynamics, in which PKA signalling negatively regulates the microtubule rescue factor CLASP to promote microtubule catastrophe, Tea[4] delivery and Pom[1] re-localization at cell sides, where Pom[1] buffers cell size upon glucose starvation
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