2. Publications
• Speriolin is a novel human and mouse
sperm centrosome protein. M. Goto, D.A.
O’Brien, E.M. Eddy. Human Reproduction, 2010
• Speriolin is a novel spermatogenic cell-
specific centrosomal protein associated
with the seventh WD motif of cdc20. M.
Goto, E.M. Eddy. JBC, 2004.
3. Functions of Speriolin
• Speriolin,a 53Kd testis-specific protein is :
Localized in the Centrosome in cytoplasm
Binding partner of cdc20 protein
Translocates cdc20 to the nucleus
Chaperones cdc20 to kinetochores during
Meiosis
Localizes to Spindle Centrioles during
Anaphase in the fertilized Oocyte
5. Functions of cdc20
• Cell cycle promoting protein:
Localizes to spindle kinetochores
Binding partner of MAD1/2 spindle
check point proteins in prometaphase
Binds to gamma tubulins of spindle
Activation of APC ligase
9. • Schematic diagram of a typical mammalian Centrosome
composed of two centrioles (mother and daughter centriole)
surrounded by a meshwork of pericentriolar material (PCM).
• Both Centrioles are connected through interconnecting fibers. The mother
Centriole is distinguished from the daughter Centriole by distal and
subdistal appendages.
• The Centrosomal material consists of a fibrous scaffolding lattice with a
large amount of coiled-coil Centrosome proteins.
• Centrosome’s three-dimensional architecture is primarily maintained through
specific protein–protein interactions.
• Microtubules are anchored with their minus ends to the Centrosome core
structure
• Microtubule growth is regulated by distal plus-end addition of tubulin subunits
Structure of Centrosome
11. • Centrosome reduction during Spermiogenesis.
• Male germ cells possess intact Centrosomes containing Centrioles and
Centrosomal proteins until the round spermatid stage (A).
• Microtubules of the distal Centriole extend as axoneme of the
spermatid tail (B).
• During Spermiation, g-tubulin and possibly other Centrosomal proteins
are disjuncted from the Centrioles and discarded with the residual
bodies (B).
• Centrioles are degenerated to various extents in spermatozoa of
different species. Rodent and snail spermatozoa lose both Centrioles
completely (C),
• Primate spermatozoa retain proximal Centrioles intact but degenerate
distal Centrioles partially (D).
• Xenopus and Drosophila spermatozoa possess both Centrioles intact (E).
Centrosome Reduction
17. Syngamy in Fertilized Oocyte: Interphase
Schatten & Sun. Molecular Human Reproduction, 2009
Nakamura et al. BOR, 2001
S-Phase
Duplication:
• Centriole
• DNA
19. • Improper Chromosome alignment on the mitotic spindle, disruption
of microtubule dynamics, or unattached kinetochores can activate
the spindle checkpoint.
• Spindle checkpoint signaling is mediated by the Bub1, Bub3,
BubR1, and Mad2 proteins, which all localize to kinetochores.
• These core spindle checkpoint regulators prevent the activator
protein cdc20 from binding to APC and therefore protects Securin, a
major APC-cdc20 target, from ubiquitin-mediated degradation. As a
result, Securin remains bound to Separase, and this prevents
cleavage of Scc1 and loss of centromeric Cohesin.
• Spindle checkpoint is relieved at the end of the metaphase by the
appropriate biorientation of the sister Chromatids at the metaphase
plate. Sensing mechanism involves detecting tension through the
Cohesin complex at the kinetochores, created by the pulling of the
spindle fibers toward the poles. Mad2 then dissociates from the
attached kinetochore, and this allows cdc20 to activate APC and
trigger sister Chromatid Segregation.
Martin D. Abeloff, MD; James O. Armitage; John E.
Niederhuber; Michael B. Kastan; W. Gillies McKenna
Abeloff’s Clinical Oncology: The Spindle Checkpoint
21. • APC, the Anaphase promoting complex :
Has Ubiquitin ligase activity
Expressed in Anaphase
Binds to and is activated by cdc20
Ubiquitinates Securin to liberate
Separase which disrupts the Cohesins
Brings about the Segregation of the
Chromosomes
Functions of APC
24. Implications
• Speriolin is the first reported testis-
specific M-protein of the PCM to be
inherited from the male gamete
• Putative role is in the regulation of Cell
Division in the 1 cell embryo during
Anaphase
• Infertility Marker-10% of IVF donors
lack sperm associated Speriolin
25. Reproductive Responsibilities of the Male Gamete
Re-organization of germ cell Chromatin so as to
maintain its Genetic & Epigenetic integrity
Transfer of the Genetic material to progeny
Transfer of the Centrioles to progeny
Transfer of Speriolin to the progeny
To produce healthy offspring
