Open Mitosis: Nuclear Envelope Dynamics 209
ing phagocytosis (Mitchison 1995; Roos 1984). Phagocytosis also would have
been a requirement for endosymbiosis, favoring the “chrononcyte” hypothe-
sis (Hartman and Fedorov 2002). In the karyomastigont hypothesis, the DNA
of the chimera recombined and remained attached to the membrane as well
as the kinetosome of its motile component, resulting in the formation of
a membrane-bound nucleus linked to cytoskeletal structures giving rise to
the kinetosome/centrosome microtubule organizing center (MTOC) facilitat-
ing mitosis (Dolan et al. 2002; Margulis et al. 2000, 2006).
2.1
Origin of Nuclear Envelope Membranes and Proteins
The nuclear membranes are thought to have evolved from or together with
the endoplasmic reticulum (ER) in the evolution of eukaryotic cells (Cavalier-
Smith 2002; Lopez-Garcia and Moreira 2006; Mans et al. 2004). This is sup-
ported by the fact that the outer nuclear envelope membrane is continuous
with the ER. It has been suggested that the radiation of the Ras-family of sig-
naling GTPases, leading to the development of the Ran cycle, played a pivotal
role in the development of a functional nuclear envelope. This hypothesis is
supported by several observations:
- The Ran cycle components are highly conserved throughout the eukary-
otic domain and are in fact the most strikingly conserved nuclear pore
components in a comparative genomics analysis, suggesting that they pre-
existed in the eukaryotic ancestor (Mans et al. 2004) - While ER vesicles show a propensity for association with chromatin to
form a rudimentary nucleus, the fusion of such vesicles docked to chro-
matin to form a continuous nuclear envelope requires the Ran cycle (Het-
zer et al. 2000, Newport and Dunphy 1992) - The nuclear pore assembly likewise requires the action of the Ran cycle
(Ryan et al. 2003, Walther et al. 2003) - The Ran cycle plays an essential role in nucleocytoplasmic transport
across the nuclear envelope (Steggerda and Paschal 2002)
Nug-type GTPases involved in ribosomal subunit export are similarly highly
conserved, suggesting that a primitive nuclear pore complex depending on
Ran and Nug GTPase-driven essential transport functions was part of the
ancestral nuclear envelope in early eukaryotic cells. Based on comparative
genomics, it has been estimated that these early nuclear pores were already
highly complex structures composed of about 20 proteins. The primordial nu-
clear import machinery likely included the karyopherins importinαandβ,
which have additional functions in spindle formation and in nuclear envelope
and pore complex assembly, respectively (Askajer et al. 2002; Harel et al. 2003;
Mans et al. 2004; Zhang et al. 2002).