Biology Reference
In-Depth Information
NuMA is a multifunctional 236 kDa protein that in interphase is a component
of the nuclear matrix, a proteinaceous network that plays a role in DNA organi-
zation. NuMA's specific roles in the nucleus are only partly understood (reviewed
in Sun and Schatten
2006
) while significantly more studies are available on
NuMA's functions as centrosome-associated protein in mitosis (reviewed in Sun
and Schatten
2006
). We do not yet know whether NuMA plays a role in sperm
DNA organization and nuclear decompaction in the zygote embryo but we know
that the nuclear matrix is important for DNA replication in the zygote (reviewed
by Yamauchi et al.
2011
; Johnson et al.
2011
). Research on the sperm's nuclear
matrix has accelerated in recent years, and it has been proposed that non-genetic
male factor infertility problems may be related to nuclear matrix instability
(reviewed in Johnson et al.
2011
), contributing to transgenerational non-genetic
instability. It has further been shown that chronic exposure of sperm to low doses
of specific toxins is correlated with an altered nuclear matrix protein profile and
includes abnormal chromatin condensation (Codrington et al.
2007a
,
2007b
) which
affects fertilization and embryo development and may also affect nuclear matrix-
centrosome interactions and nuclear-centrosome synchronization. This and other
examples indicate the effects of non-genetic components on the nuclear matrix that
may affect synergistic interactions with centrosomes and may have implications in
male factor infertility.
NuMA is an important link in synchronizing nuclear and centrosome matura-
tion events after fertilization; studies in somatic cells have shown that NuMA
requires precise regulation including regulation by cyclin B to move out of the
nucleus into the cytoplasm during prophase and associate with mitotic centro-
somes to stabilize centrosome-microtubule interactions for the formation of the
mitotic apparatus. NuMA is not associated with the interphase centrosome; it
strictly serves as nuclear protein in interphase and becomes a centrosome-asso-
ciated protein only in mitosis (reviewed in Sun and Schatten
2006
). NuMA is
highly insoluble in the nucleus but at the time of nuclear envelope breakdown
NuMA becomes hyperphosphorylated by p34
cdc2
which allows dispersion of
NuMA into the cytoplasm and subsequent translocation to the spindle poles in a
dynein-mediated process. NuMA remains associated with the spindle poles until
anaphase; it dissociates from spindle poles after dephosphorylation as a result of
Cdk1 inactivation and loss of cyclin B that occurs by proteasome-mediated deg-
radation (Gehmlich et al.
2004
).
Most of the studies on NuMA have been performed in somatic cells while only
a few detailed studies are available for embryonic cells. Our recent studies in
human oocytes showed a requirement for dynein to mediate NuMA translocation
to the spindle poles during first mitosis (Alvarez Sedó et al.
2011
; Schatten et al.
2012
). In the MI and MII meiotic spindles NuMA was localized to the meiotic
spindle poles and displayed abnormalities in aged oocytes. It also displayed
abnormalities in fertilized oocytes in which sperm decondensation failed which
coincided with abnormal NuMA immunofluorescence staining patterns and sug-
gests that NuMA abnormalities are associated with fertilization failures. Dispersed
NuMA fluorescence staining patterns were seen in male and female pronuclei in
