Vertebrate Development Maternal to Zygotic Control (Advances in Experimental Medicine and Biology)

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10.3 Maternal Protein Degradation


Almost every discussion of maternal factors regulating OET puts into the spotlight
maternal mRNAs, while much less attention is paid to proteins. This is understand-
able because analysis of maternal mRNAs is much easier in terms of experimental
approaches and the amount of required material. Undeniably, maternal mRNA
control is an important aspect of OET; however, it must be recognized that OET is
executed by proteins, not by mRNAs per se. Accordingly, this section is devoted to
maternal proteins and their degradation.
Numerous studies suggest that protein degradation by the ubiquitin-proteasome
pathway is essential for OET (reviewed in DeRenzo and Seydoux 2004 ). There is
also a growing amount of high-throughput data concerning protein dynamics during
OET. Here, we will review the current knowledge of maternal proteome elimination
after fertilization, including degradation mechanisms, model examples, and recent
proteome-wide data.
Maternal protein degradation has two roles: (1) nourishing the early embryo by
releasing amino acids from maternal protein stores, prominent in oocytes with large
yolk deposits (yolk is discussed in the Sect. 10.5.2), and (2) transforming the oocyte
into a totipotent zygote by removing proteins that confer oocyte identity. There are
two major pathways for protein degradation in vertebrate cells: (1) autophagy-
mediated lysosomal degradation and (2) ubiquitin-proteasome pathway


10.3.1 Autophagy-Mediated Lysosomal Degradation


During OET


Autophagy (reviewed in Mizushima 2007 ) is a bulk degradation system. During
autophagy, a portion of cytoplasm is sequestered into an autophagosome, which
fuses with a lysosome, resulting in degradation of the engulfed material. As
such, the role of autophagy during OET would lay in general protein turnover,
amino acid recycling, and structural rearrangements in the zygote rather than in
specific protein targeting.
Autophagy is important in many cellular processes as well as for early develop-
ment in mice. Formation of autophagosomes is upregulated immediately after fer-
tilization, and early embryos contain a large number of lysosomes (Tsukamoto
et al. 2008 ). Increased autophagy in zygotes is induced by fertilization; it is not
induced by starvation in unfertilized ovulated eggs (Tsukamoto et al. 2008 ).
Functional significance of autophagy in mouse development was shown in mice
lacking Atg5, an essential factor for autophagosome formation (Mizushima et al.
2001 ). Remarkably, Atg5−/− mice obtained by crossing heterozygotes develop until
birth (Mizushima et al. 2001 ), but Atg5−/− embryos lacking the maternal pool of
ATG5 exhibit an early embryonic arrest (4-/8-cell stage), while Atg5−/− oocytes
fertilized with a wild-type sperm develop to term (Tsukamoto et al. 2008 ). These


P. Svoboda et al.

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