Moonlighting Function of the Tubulin Cytoskeleton: Macromolecular Architectures in the Cytoplasm - Systems Biology of Metabolic and Signaling Networks - page 161

7.1 Macromolecular Associations
Cell compartments are crowded with solutes, soluble macromolecules such as
enzymes, nucleic acids, and structural proteins, and membranes to create complex
structures that continue to be discovered (Fridman et al. 2012 ). The high protein
density within the large compartments of the cells predominantly determines major
characteristics of cellular environment such as viscosity, diffusion, and heterogene-
ity. The fact that the solvent viscosity of cytoplasm is not substantially different from
that of water is explained by intracellular structural heterogeneity: macromolecular
density is relatively low within the interstitial voids in the cell because many soluble
enzymes are apparently integral parts of the insoluble cytomatrix and/or cytoskeletal
ultrastructures. In other words, macromolecules are not distributed homogeneously
and the cell should not be considered as a “bag.” Indeed, most of the cytoplasmic
proteins have nondiffusing forms or diffuse on the timescale of hours as evidenced
by high voltage electron microscopy [(Ovadi and Saks 2004 ) and refs therein].
The eukaryotic cytoskeleton, which consists of three filamentous systems, has
many physiological and pathological functions. The dynamic reorganizing ability
of the filamentous structures is highly variable in different cells and tissues; the
precise regulation of microtubular dynamics is critical for cell cycle progression,
cell signaling, intracellular transport, cell polarization, and organismal develop-
ment. The dynamic instability of microtubules in living cells has been analyzed by
microscopy of microinjected or expressed fluorescent tubulin, time-lapse micros-
copy, and analysis of time-dependent, microtubule length changes (Kamath
et al. 2010 ). The multiple functions of these superstructures are achieved by the
static and dynamic associations of macromolecules and ligands, and by posttrans-
lational modifications. In fact, macromolecular associations resulting from
crowding (Swaminathan et al. 1997 ) create intracellular superstructures such as
the microtrabecular lattice which is formed by the organization of the microtubule
systems while the soluble enzymes are integral parts of the cytomatrix, a cytoplas-
mic association of enzymes (Minton and Wilf 1981 ; Porter et al. 1983 ). The full
range of ultrastructures and functions characteristic of the cytoskeleton and, in
particular, the microtubule system has only been found so far in eukaryotes.
However, different types of filamentous structures have been identified in
prokaryotes (Ingerson-Mahar and Gitai 2012 ).
One of the best understood of prokaryotic filaments is the tubulin-like FtsZ
protein. This protein assembles into a ring-like structure, the Z-ring, at the site of
cell division (Errington et al. 2003 ; Romberg and Levin 2003 ). FtsZ can also
assemble into helices, of unknown function, that are highly dynamic (Thanedar
and Margolin 2004 ). The FtsZ protein has a structural homology to tubulin
(Lowe and Amos 1998 ). In vitro, FtsZ can form a wide variety of polymeric
structures, some of which may resemble eukaryotic microtubules, depending on
the presence and concentrations of lipids, divalent ions, GTP, and other proteins
(Alexandre et al. 2002 ; Gonzalez et al. 2005 ; Popp et al. 2010 ; Gundogdu
et al. 2011 ;Hsinetal. 2012 ; Martin-Garcia et al. 2012 ; Hou et al. 2012 ). As in