bioRxiv ScienceSearch

bioRxiv · 10.1101/648436

A single light-responsive sizer can control multiple-fission cycles in Chlamydomonas

Abstract

Proliferating cells need to coordinate cell division and growth to maintain size homeostasis. Any systematic deviation from a balance between growth and division results in progressive changes of cell size over subsequent generations. While most eukaryotic cells execute binary division after a mass doubling, the photosynthetic green alga Chlamydomonas can grow more than eight-fold during daytime before undergoing rapid cycles of DNA replication, mitosis and cell division at night, which produce up to 16 daughter cells. Here, we propose a mechanistic model for multiple fission and size control in Chlamydomonas. The model comprises a light-sensitive and size-dependent biochemical toggle switch that acts as a sizer and guards transitions into and exit from a phase of cell-division cycle oscillations. We show that this simple sizer-oscillator arrangement reproduces the experimentally observed features of multiple-fission cycles and the response of Chlamydomonas cells to different light-dark regimes. Our model also makes testable predictions about the dynamical properties of the biochemical network that controls these features and about the networks makeup. Collectively, these results provide a new perspective on the concept of a commitment point during the growth of Chlamydomonas cells and hint at an intriguing continuity of cell-size control in different eukaryotic lineages.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC=\"FIGDIR/small/648436v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (35K):\norg.highwire.dtl.DTLVardef@48f9corg.highwire.dtl.DTLVardef@170625eorg.highwire.dtl.DTLVardef@14a20a0org.highwire.dtl.DTLVardef@1a3ff9a_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIG1-sizer and S/M-oscillator can give rise to multiple-fission cycles in Chlamydomonas\nC_LIO_LILight-responsive bistable switch may guard transition between G1 and S/M-cycles\nC_LIO_LIIllumination increases S/M-entry threshold, causing multiple-fission cycles\nC_LIO_LIDark shift lowers S/M-entry threshold, allowing small cells to commit to fewer divisions\nC_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Heldt, F. S., Tyson, J. J., Cross, F. R., Novak, B.. 2019-05-27. A single light-responsive sizer can control multiple-fission cycles in Chlamydomonas. https://doi.org/10.1101/648436

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Functional characterization of Rho GTPase activating proteins SYDE1 and SYDE2

The human genome encodes more than 60 proteins containing Rho GTPase activating protein (RhoGAP) domains, many of which remain understudied with respect to their target specificity and biological roles. SYDE1 and SYDE2 are two such orphan RhoGAPs, for which there are few studies characterizing their biochemical and cellular functions and conflicting reports identifying their cognate GTPases. We previously identified SYDE1 and SYDE2 in a screen for substrates of the c-Jun N-terminal kinases. Here, we show that SYDE1 and SYDE2 are preferentially phosphorylated by JNK1 relative to other mitogen-activated protein kinases (MAPKs) at sites proximal to a kinase docking region. Purified SYDE1 and SYDE2 are shown to have significant catalytic GAP activity toward RhoA, Rac1, and Cdc42. However, neither up- nor down-regulation of SYDE1/2 expression leads to detectable changes in bulk GTP loading of any of these GTPases. Nevertheless, we demonstrate that SYDE1 and SYDE2, in a partially GAP-dependent manner, increase cell spreading and number of focal adhesions, and promote more directionally persistent migration in HEK293 cells. Together, these findings establish SYDE1 and SYDE2 as robust JNK substrates with catalytic activity toward a set of Rho GTPases and reveal basic functions of SYDE1 and SYDE2 in regulating cell morphology, adhesion, and migration.

cell biology

The filopodial scaffold polyphosphate dictates cell adhesion-versus-invasion decisions

Inorganic polyphosphate (polyP) is an ancient polymer conserved across all life, serving cell type and location specific functions in every major compartment. Yet its role at the plasma membrane, where it accumulates to peak levels in many primary cells, is largely unknown. Here we identify polyP as a stabilizing component of filopodia, actin based membrane protrusions that govern cell adhesion, contact inhibition, and chemotaxis. Elevating cellular polyP increases filopodial stability and enhances cell adhesion, whereas reducing polyP accelerates filopodial disassembly and promotes cell migration. Mechanistically, we find that polyP acts as a structural filopodial scaffold, recruiting and organizing IRSp53, a membrane curvature inducing protein. We show that metastatic fibroblasts and breast cancer organoids carry markedly reduced and intracellularly reorganized polyP levels relative to their non transformed counterparts. Restoring endogenous polyP via lipid nanoparticle delivery suppresses their invasive phenotypes and reverses prometastatic gene expression signatures, implicating polyP as a primordial tumor suppressor.

cell biology

Mitochondrial transfer mediates metabolic communication between beta cells and islet macrophages

Pancreatic islet macrophages support islet homeostasis and adapt their metabolic program in response to environmental cues, including beta cell released factors. Intercellular mitochondrial transfer is a biological process that modulates cellular responses. To test whether beta cells, which are strongly secretory, transfer mitochondria to islet macrophages, we generated mice with beta cell-specific expression of mitochondrial GFP (PhAMfloxIns1Cre). We demonstrate that beta cells transfer mitochondria to islet macrophages in vivo and in vitro. Diabetogenic stressors did not alter the frequency of mitochondrial transfer and macrophages containing beta cell-derived GFP exhibit increased protein synthesis rates. RNA-seq identified upregulation of activity-regulated cytoskeleton associated protein (Arc) in macrophages receiving beta cell-derived mitochondria, while disruption of actin cytoskeleton dynamics prevented mitochondrial transfer. Together, these findings identify mitochondrial transfer as a previously unrecognized mechanism of beta cell-macrophage communication that may contribute to islet homeostasis and immune regulation.

cell biology