Worm Breeder's Gazette 10(3): 23

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Yolk Proteins and Lipids

William Sharrock

Figure 1

A number of observations on yolk proteins suggest that their primary 
biological function is lipid transport and sorting.  It has been known 
for some time that the yolk proteins of vertebrates form dimeric 
lipoprotein complexes containing 15-20% lipid.  But there was no 
obvious parallel between the vertebrate yolk polypeptides - two 
lipovitellins and phosvitin - and the four C.  elegans yolk proteins - 
yp170A, yp170B, yp115, and yp88.  Recently, Nardelli et al. (1) 
compared the vitellogenin genes from frog and chicken with the vit-5 
gene from C.  elegans and found substantial amino acid sequence 
similarities in many regions of the proteins.  The exception is the 
phosvitin domain, which is not present in the nematode vitellogenins.
Work in my laboratory has now produced a model of native yolk 
protein structures in C.  elegans that confirms the conservation of 
higher-order yolk lipoprotein structure over the evolutionary interval 
separating nematodes from vertebrates.  There are at least two 
distinct lipoprotein complexes in C.  elegans.  Both resemble the 
vertebrate complexes in that they are fundamentally dimeric, have 
relative molecular masses of about 480,000, and carry about 20% lipid, 
a mixture of phospholipids, triglycerides, and unidentified minor 
lipids.  There is a twist, though.  One of the C.  elegans 
lipoproteins seems to be a simple homodimer of yp170B (the B dimer), 
resembling the vitellogenin dimers of vertebrates.  But the other 
complex is apparently composed of yp170A, yp115, and yp88 (the A 
complex).  It still has the properties of a dimer, suggesting that 
yp115 and yp88 together form a single monomeric functional unit 
equivalent to either of the yp170s.  This is consistent with their 
origin in a single primary translation product, encoded by the vit-6 
gene.  The diagram below summarizes the model in the general context 
of vitellogenesis.
[See Figure 
It should be emphasized that this is a model.  It accounts for the 
physical properties of yolk protein particles and for the results of 
immunoaffinity binding experiments, postulating only two mutually 
exclusive sets of protein-protein interactions.  It is not possible, 
however, to exclude rigorously the existence of other combinations of 
the yolk polypeptides - a yp170A homodimer, for example, or a vit-6 
'dimer' containing two each of yp115 and yp88.
The sequence similarities detected by Nardelli et al.  suggest that 
functional constraints have dictated the conservation of certain yolk 
protein characteristics in the evolution of birds and amphibians from 
invertebrates: the binding of lipids, the pairing of yolk lipoproteins 
in dimeric complexes, and the positions of cysteine residues.  The 
binding of lipid appears to be a relatively autonomous function of the 
monomeric units.  It's unclear, then, what advantage is gained by 
association of monomeric lipoproteins in dimers, but part of the 
reason for cysteine conservation seems to be the formation of 
intermolecular disulfides between the two halves of the dimers.  There 
are indications of cross-linking between yp170A and yp88 in the A 
complex, and between the two yp170B polypeptides in the B dimer.  
Other cysteines are apparently involved in intramolecular disulfides.
The association of yolk proteins with lipids suggests that lipid 
transport may be the primary function of yolk proteins.  Because early 
embryogenesis in C.  elegans and many other organisms proceeds 
essentially by subdivision of the zygote into progressively smaller 
membrane-bounded compartments, fairly large amounts of lipid are 
required for new membrane assembly.  It may be advantageous to provide 
a maternally synthesized reserve of lipids so that everything doesn't 
have to be made up from simple precursors in the embryo.  Such a lipid 
transport and storage role could explain the apparent variation of 
yolk protein utilization rates in C.  elegans embryos (2).  Yolk 
protein antigens seem to disappear from the anterior of the embryo, 
where cells are small and densely packed (hence, have a high 
proportion of membrane surface to volume) while they are retained in 
the intestine (large cells, with lower surface to volume ratio).
The problems of moving lipids around in cells and organisms are 
universal.  In fact, vitellogenins seem to be structurally related to 
at least one human serum apolipoprotein.  Baker (3) has detected 
sequence similarities between vertebrate and nematode vitellogenins 
and human apolipoprotein B-100, the apoprotein of low-density 
lipoprotein (LDL).  These homologies are sufficiently strong to imply 
that the human protein evolved, at least in part, from yolk proteins.  
Further, like LDL, vitellogenins are synthesized by the liver or 
intestine, bind to a specific receptor, and are endocytosed by the 
target cell.  The big difference between yolk lipoproteins and serum 
lipoproteins may be that yolk proteins, with their bound lipid, are 
temporarily sequestered in yolk organelles after endocytosis, and are 
degraded only later, when the lipid reserves are needed.

Figure 1