Interaction between EB1 and p150glued Is Required for Anaphase Astral Microtubule Elongation and Stimulation of Cytokinesis

Abstract

In animal cells, microtubules (MTs) of the mitotic apparatus (MA) communicate with the cell cortex to stimulate cytokinesis; however, the molecular nature of this stimulus remains elusive . A signal for cytokinesis likely involves the MT plus end binding family of proteins, which includes EB1, p150glued, APC, LIS1, and CLIP-170. These proteins modulate MT dynamics and facilitate interactions between growing MTs and their intracellular targets, including kinetochores, organelles, and the cell cortex . The dynein-dynactin complex mediates many of these microtubule capture events . We report that EB1 and p150glued interactions are required for stimulation of cytokinesis in dividing sea urchin eggs. Injected antibodies against EB1 or p150glued suppressed furrow ingression but did not prevent elongation of anaphase astral MTs toward the cortex, suggesting that EB1 and dynactin are both required for communication between the MA and the cortex. Targeted disruption of the interaction between EB1 and p150glued suppressed anaphase astral MT elongation and resulted in a delay of cytokinesis that could not be overcome by manipulation of the asters toward the cortex. We conclude that EB1 and dynactin participate in stimulation of the cleavage furrow, and their interaction promotes elongation of astral MTs at anaphase onset.

The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis

“…Proteins recruited to MT plus ends can anchor MTs to specific cellular structures and control MT dynamics ( Kumar and Wittmann, 2012;Mimori-Kiyosue et al, 2005Strickland et al, 2005). In this respect, tethering of Centralspindlin to the plus ends of equatorial astral microtubules enables it to play a role in regulating MT stability and MT anchoring at the cortex during cytokinesis.…”

“…Binding is dependent upon the SxIP motif and electrostatic interactions between positively charged residues that flank the SxIP motif and negatively charged residues on EB1 (Honnappa et al, 2009). +TIP proteins that bind to MTs through EB1 can anchor MTs to specific cellular structures and control MT dynamics, including those during cytokinesis (Kumar and Wittmann, 2012;Mimori-Kiyosue et al, 2005Strickland et al, 2005). We identified a putative SxIP motif in Mgc and propose that it is functionally important for the localization of Mgc to the plus ends of equatorial astral MTs during cytokinesis and for its MT-dependent localization to cell-cell junctions.…”

Liver tetraploidization is controlled by a new process of incomplete cytokinesis

“…5B). Furthermore, we analyzed localization of EB1, a protein that only associates with elongating microtubules and not with microtubules that become stabilized upon contact with the cortex (Strickland et al, 2005). We observed that the equatorial cortical EB1 staining was weak in hepatocytes that completed cytokinesis (Fig.…”

Dynactin targets Pavarotti-KLP to the central spindle during anaphase and facilitates cytokinesis inDrosophilaS2 cells

“…Glued promotes the elongation of astral microtubules to facilitate furrow ingression during cytokinesis (Strickland et al, 2005).…”

“…In human cells, this regulation depends on association with EB1 and is essential to maintain the radial arrays of microtubules in interphase cells (Askham et al, 2002;Strickland et al, 2005). A recent study further proposed that the interaction between EB1 and p150…”