Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry

Abstract

Proper coupling of centrosomes to the nuclear surface at prophase is essential for fidelity of mitotic events. A pool of dynein motors anchored to the nuclear surface mediates this step. The protein Asunder is required in human cultured cells for dynein localization and tethering of centrosomes to the nucleus at mitotic entry.

Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex

“…Consistent with our previous report, we found that 78% of nontargeting (NT) control siRNA cells had a striking enrichment of dynein on the NE after brief nocodazole treatment (Figure 1, A and O); in contrast, the percentage of cells with perinuclear dynein was reduced to 20% after hASUN depletion (Figure 1, C and O; Jodoin et al. , 2012).…”

“…In both Drosophila spermatocytes and cultured human cells, we previously identified ASUN as an additional regulator of dynein recruitment to the NE at G2/M of meiosis and mitosis, respectively, although physical interaction between ASUN and dynein has not been demonstrated (Anderson et al. , 2009; Jodoin et al. , 2012).…”

“…On the basis of these temporal associations of the localizations of ASUN and perinuclear dynein, we previously proposed that the cytoplasmic pool of ASUN likely mediates recruitment of dynein motors to the NE (Anderson et al. , 2009; Jodoin et al. , 2012).…”

Dynein Recruitment to Nuclear Pores Activates Apical Nuclear Migration and Mitotic Entry in Brain Progenitor Cells

“…NE dynein has been reported to facilitate NE breakdown (NEB) (Beaudouin et al, 2002; Hebbar et al, 2008; Salina et al, 2002) and tether the nascent mitotic spindle to the NE for pole separation (Raaijmakers et al, 2012) and efficient chromosome capture (Bolhy et al, 2011; Jodoin et al, 2012; Splinter et al, 2010). Dynein is linked to the NE via interactions originating from two distinct nuclear pore components (Figure 1A–1B).…”

Breaking down the wall: the nuclear envelope during mitosis

“…By disrupting this connection, a series of recent studies has elegantly shown that association of the centrosome with the NE is important not only for NEBD but also for rapid assembly of a spindle and chromosome biorientation. In most cells, centrosome tethering relies on dynein localization to the NE [56][57][58][67][68][69][70]. Multiple lines of evidence linking the SUN/KASH proteins to centrosome tethering come from different organisms, including C. elegans.…”