Biology subjects

Costa, K.

Publications and source records attributed to Costa, K..

3 recordsLinked to original sources

bioRxiv2020

Interactions between axon-like projections extended by Drosophila Follicle Stem Cells dictate cell fate decisions

Stem cells cycle between periods of quiescence and proliferation to promote healthy tissue aging. Once proliferation is initiated, mechanisms that control the balance between self-renewal and differentiation must be engaged to ensure maintenance of stem cell pools until the next quiescent cycle occurs. Here, we demonstrate that dynamic axon-like projections extended by Follicle Stem Cells (FSCs) in the Drosophila ovary control the self-renewal-differentiation balance. Known axon growth regulators still life and sickie are necessary and sufficient for FSC projection growth, mediating organization of germline cyst architecture during follicle formation, controlling targeting of projections to FSCs or germ cells, and regulating expression of the cell fate determinants Eyes Absent (Eya) and Castor (Cas). Our results support a model in which FSC projections function similarly to axons, providing structural organization to a dynamic organ while mediating communication between distinct cell types to effect the key cell fate decision to self-renew or differentiate.

developmental biology↗

bioRxiv2020

The mechanism of motor inhibition by microtubule-associated proteins

Microtubule (MT)-associated proteins (MAPs) regulate intracellular transport by selectively recruiting or excluding kinesin and dynein motors from MTs. We used single-molecule and cryo-electron imaging to determine the mechanism of MAP-motor interactions in vitro. Unexpectedly, we found that the regulatory role of a MAP cannot be predicted based on whether it overlaps with the motor binding site or forms liquid condensates on the MT. Although the MT binding domain (MTBD) of MAP7 overlaps with the kinesin-1 binding site, tethering of kinesin-1 by the MAP7 projection domain supersedes this inhibition and results in biphasic regulation of kinesin-1 motility. Conversely, the MTBD of tau inhibits dynein motility without overlapping with the dynein binding site or by forming tau islands on the MT. Our results indicate that MAPs sort intracellular cargos moving in both directions, as neither dynein nor kinesin can walk on a MAP-coated MT without favorably interacting with that MAP. HIGHLIGHTSO_LIMAP7 binds to a novel site and can coexist with tau on the MT. C_LIO_LIKinesin-1 motility is biphasically regulated by MAP7 accumulation on the microtubule. C_LIO_LIMT decoration of MAPs inhibits motors even when they do not block the motor binding site. C_LIO_LIMotors need to interact with a MAP to walk on MAP-decorated MTs C_LI

biophysics↗

bioRxiv2020

SARS CoV-2 nucleocapsid protein forms condensates with viral genomic RNA

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes COVID-19, a pandemic that seriously threatens global health. SARS-CoV-2 propagates by packaging its RNA genome into membrane enclosures in host cells. The packaging of the viral genome into the nascent virion is mediated by the nucleocapsid (N) protein, but the underlying mechanism remains unclear. Here, we show that the N protein forms biomolecular condensates with viral genomic RNA both in vitro and in mammalian cells. Phase separation is driven, in part, by hydrophobic and electrostatic interactions. While the N protein forms spherical assemblies with unstructured RNA, it forms asymmetric condensates with viral RNA strands that contain secondary structure elements. Cross-linking mass spectrometry identified a region that forms interactions between N proteins in condensates, and truncation of this region disrupts phase separation. We also identified small molecules that alter the formation of N protein condensates. These results suggest that the N protein may utilize biomolecular condensation to package the SARS-CoV-2 RNA genome into a viral particle.

biophysics↗