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material in the cytoplasm, and the lack of a membrane around the granule, which
together provide partial isolation but also allows continued interaction with the
cytoplasm.
How are mRNP granule components maintained separated from the cytoplasm?
One emerged strategy is the utilization of a hydrogel granule scaffold. A hydrogel
can form by polymerization of substrate molecules that generate a meshwork with
a viscosity similar to that of glycerol (Brangwynne et al. 2009a; Han et al. 2012 ;
Toretsky and Wright 2014 ). The hydrogel is thus less soluble than the generally
more liquid cytoplasm (Brangwynne et al. 2009a; Han et al. 2012 ; Toretsky and
Wright 2014 ). The hydrogel’s viscous meshwork can provide a scaffold to hold the
mRNP granule content together (Brangwynne et al. 2009a; Han et al. 2012 ; Toretsky
and Wright 2014 ). Such a condensation of the granule material would keep it physi-
cally separated from the remaining liquid cytoplasm. This separation, however,
needs to be partial, since mRNP granules have the capacity to both assemble and
disassemble under certain conditions. Therefore, the physical separation of granules
that enables their function must be balanced with the ability of cytoplasmic factors
to interact with the granules for both their trafficking and disassembly at the right
time and place. Indeed, the phosphorylation state of the hydrogel-forming mole-
cules can regulate their condensation-dissolution state (Wang et al. 2014 ).
One type of molecule that can form hydrogels is the nucleoporin family of pro-
teins that build the nuclear pore complexes (NPC). Nucleoporins contain multiple
FG repeat domains. The FG domains of nucleoporins in the NPC are found as loop-
ing extensions from the NPC into the vicinity of the pore, forming a complex mesh-
work. It has been demonstrated that this meshwork of nucleoporins actually forms
a hydrogel that functions as a barrier (Hulsmann et al. 2012 ). Nuclear export/import
factors are thus required to interfere with the hydrogel bonds to allow for passage of
their cargo. Indeed, specific nucleoporins were able to form hydrogels in vitro,
which depended on the FG repeat domains (Frey et al. 2006 ).
For C. elegans embryonic germplasm P granules, important studies have demon-
strated the mechanism for the formation and dissolution of these mRNP granules
(Brangwynne et al. 2009a; Wang et al. 2014 ). Embryonic P granules segregate
along the anteroposterior axis in early cleavage embryos to specify the germ line
cell. The segregation of P granules to the posterior of the embryo was shown to be
a result of a condensation-dissolution gradient (Brangwynne et al. 2009b). In the
posterior, granule components are allowed to condense and phase separate into a
liquid droplet glycerol-like consistency, forming granules. In the anterior, however,
conditions favor the dissolution of granule components into the cytoplasm and
therefore granule disassembly. The conditions regulating the condensation/dissolu-
tion states turned out to be protein phosphorylation (Wang et al. 2014 ).
The substrate forming the hydrogel-like structure in P granules was found to be the
MEG family of proteins (Wang et al. 2014 ). The MEG proteins are intrinsically disor-
dered proteins (IDPs), i.e., proteins that contain long stretches of residues that do not
autonomously fold into any specific structure but remain random in orientation. In high
concentration, IDPs have been suggested to promote the phase separation of mRNP
granules (Toretsky and Wright 2014 ), similar to the FG repeats. Direct phosphorylation
M. Escobar-Aguirre et al.