Synthetic Par polarity induces cytoskeleton asymmetry in unpolarized mammalian cells.
Cell
; 186(21): 4710-4727.e35, 2023 10 12.
Article
in En
| MEDLINE
| ID: mdl-37774705
ABSTRACT
Polarized cells rely on a polarized cytoskeleton to function. Yet, how cortical polarity cues induce cytoskeleton polarization remains elusive. Here, we capitalized on recently established designed 2D protein arrays to ectopically engineer cortical polarity of virtually any protein of interest during mitosis in various cell types. This enables direct manipulation of polarity signaling and the identification of the cortical cues sufficient for cytoskeleton polarization. Using this assay, we dissected the logic of the Par complex pathway, a key regulator of cytoskeleton polarity during asymmetric cell division. We show that cortical clustering of any Par complex subunit is sufficient to trigger complex assembly and that the primary kinetic barrier to complex assembly is the relief of Par6 autoinhibition. Further, we found that inducing cortical Par complex polarity induces two hallmarks of asymmetric cell division in unpolarized mammalian cells spindle orientation, occurring via Par3, and central spindle asymmetry, depending on aPKC activity.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cytological Techniques
/
Cell Polarity
/
Adaptor Proteins, Signal Transducing
/
Mitosis
Limits:
Animals
Language:
En
Year:
2023
Type:
Article