Does NuMA have a scaffold function in the interphase nucleus?

We review the properties of NuMA, concentrating on a possible role for NuMA as a scaffold protein in the interphase nucleus. NuMA is a component of the nuclear matrix in interphase cells and translocates to the spindle poles in mitosis. NuMA has a secondary structure in which a long central rod domain that forms a double-stranded coiled coil is flanked by globular terminal domains. In vitro assembly experiments with bacterially expressed recombinant protein showed that NuMA seems not to form filaments, but instead builds multiarm oligomers by interaction of the C-terminal globular domains. Transient overexpression of NuMA in HeLa cells induced the formation of a three-dimensional lattice with a quasihexagonal organization that fills the nucleus. Use of mutant constructs showed that the lattice spacing depended on the length of the rod domain. Using a 12-arm oligomer as the structural unit, computer modeling can explain the observed nuclear lattices. The flexibility of the NuMA molecule as well as its dynamic capacity to form lattices is a hint that NuMA may play a structural role in the architecture of the normal interphase nucleus.