PgmNr C65: Role of Aurora Kinases in Single-Cell Regeneration of Stentor.

Authors:
A. Lin; W. Marshall


Institutes
UCSF, San Francisco, CA.


Abstract:

Single cells are capable of developing complex patterns and shapes, but the mechanism by which cells develop shape is largely unknown. Stentor coeruleus is a classical model system to study the development and regeneration of cell shape due to the large size (1mm3), the presence of distinct cortical features that define body axes, and most importantly due to the fact that we can surgically manipulate the cells and visualize their regeneration.  When the oral apparatus is regenerated in Stentor, the macronucleus undergoes shape changes identical to those that occur during cell division at the point in division when a new oral apparatus is formed.   This observation has suggested that the timing of distinct steps of oral apparatus formation might be regulated by the same molecules that regulate the timing of division, possibly suggesting that mitosis mechanisms are integral to the processes of regeneration. To study whether there is a connection between regeneration and mitosis, we looked at the role of Aurora kinases in regeneration. Aurora kinase A (AurkA) is a kinase known to regulate spindle assembly. Aurora kinase B (AurkB) is known to guide kinetochore attachment to the spindle. We studied the role of AurkA and AurkB in single-cell regeneration using Aurora kinase inhibitors. We have observed that AurkA inhibitor, MLN8237 and VX-680, accelerates regeneration. Surprisingly, AurkA and AurkB inhibitor, PF03814735, suppresses regeneration entirely. Thus, we show that Aurora kinases are involved in single cell-regeneration and a link between regeneration and mitosis.