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Abstract:
Cytokinesis involves constriction of the cell at the equator. Without
decreasing in volume, a spherical cell requires a net increase in the surface area
during this constriction. The constriction is driven by formation of an actomyosin
contractile ring, and the surface increase by addition of membrane during the
formation of the cleavage furrow. Both events depend on the central spindle
microtubules at the midzone of the spindle and, in particular, on the centralspindlin
protein complex. The communication between the central spindle microtubules and
the actomyosin ring involves binding of a GAP and a GEF for RhoA to the
centralspindlin kinesin Pavarotti/MKLP1. However, it is still unclear which molecular
machinery connects the mitotic spindle to membrane trafficking during cleavage
furrow ingression.
ARF6 is a member of the ARF family of small GTPases, and previous
studies suggest that it is an important regulator of membrane trafficking through the
endocytic pathway, and cortical Actin remodelling. I generated an arf6 null mutant in
Drosophila. arf6 null mutants survive to adulthood without obvious morphological
defects, indicating that ARF6 is not required for Drosophila somatic development.
However, ARF6 is required for cytokinesis in Drosophila spermatocytes. The
centralspindlin kinesin Pavarotti, identified as an ARF6 interactor in a Yeast-2-Hybrid
assay, binds ARF6 in GST pulldowns, and interacts genetically with the arf6 mutant.
ARF6 localizes to the plasma membrane and a population of early and recycling
endosomes. During cytokinesis, ARF6 is enriched on recycling endosomes at the
central spindle. arf6 mutants form a cleavage furrow during cytokinesis, which later
regresses. Cytokinesis in arf6 mutant spermatocytes lacks the rapid plasma membrane
expansion observed during normal divisions.
The results of this study suggest that ARF6 might promote rapid recycling of
endosomal membrane stores at the central spindle to the plasma membrane during
cytokinesis. ARF6 might be recruited to the central spindle via its interaction with
Pavarotti, and act as part of the molecular link between the central spindle
cytoskeleton and the rapid plasma membrane addition necessary for cytokinesis.