Turgay et al. reveal that SUN proteins help disassemble the nuclear envelope at the start of mitosis and promote assembly of the mitotic spindle during metaphase.
Early in mitosis, the microtubule-based motor protein dynein binds to the nuclear envelope to promote its breakdown and dispersal. Several proteins recruit dynein to nuclear pores during prophase, but, because nuclear pore complexes start to disassemble at the end of this phase, additional proteins may be required to recruit dynein to the nuclear envelope/ER network as cells progress into prometaphase. Inner nuclear membrane SUN proteins, in partnership with outer nuclear membrane KASH proteins, tether dynein to the nuclear envelope to support nuclear migration in interphase cells, but whether they assist membrane remodeling during mitotic entry was unknown.
Turgay et al. found that HeLa cells lacking both SUN1 and SUN2 recruited less dynein to the nuclear envelope during prophase. Accordingly, the cells formed fewer prophase nuclear envelope invaginations, a sign that dynein-dependent membrane remodeling was reduced. The SUN-deficient cells also took longer to clear their nuclear membranes away from chromosomes during prometaphase, indicating that SUN proteins are required to recruit dynein throughout early mitosis, presumably in conjunction with KASH family proteins.
After nuclear envelope breakdown, SUN1 and SUN2 disperse into the ER that surrounds the mitotic spindle. Surprisingly, SUN-deficient cells formed misoriented and disorganized spindles with fragmented centrosomes. Senior author Ulrike Kutay now wants to investigate how long SUN–KASH complexes persist during mitosis and how SUN proteins promote the organization of mitotic spindles.