Biology Reference
In-Depth Information
Fig. 7.3
Moonlighting
function of TPPP/p25. (a): colocalization of EGFP-TPPP/p25 with the
microtubule network (
red
) detected by immunofluorescence; (b): co-enrichment of TPPP/p25 and
α
-synuclein in human pathological inclusion visualized by immunohistochemistry of human
pathological brain tissue for
α
-synuclein
tissue characteristic of synucleinopathies (Kovacs et al.
2004
). This protein is
primarily expressed in oligodendrocytes where the tubulin polymerization pro-
moting and microtubule bundling activity of TPPP/p25 are crucial for the
development of projections in the course of differentiation of the progenitor
cells leading to myelinization, requiring the ensheathment of axons for their
normal function in the central nervous system (CNS) (Fig.
7.3
). However, its
function is entirely different when it is co-localizedandconcentratedinneurons
or glia cells with
α
-synuclein forming pathological inclusions such as Lewy
bodies (Ovadi
2011
).
Moonlighting proteins display autonomous, markedly different, functions such
as structural and catalytic functions that are sometimes unrelated. Their interactions
are particularly characteristic of disordered proteins. One of their characteristic
features is that they use regions outside the active site for other functions, such as
regulatory and structural functions (Khersonsky and Tawfik
2010
). Moonlighting
proteins are present in diverse organisms (Huberts and van der Klei
2010
), and the
implications of their different functions should be considered when trying to
explain the multiple symptoms of single-gene disorders or
to predict
the
consequences of metabolic engineering (Flores and Gancedo
2011
)
Diseases resulting from disordered proteins require unconventional approaches
that do not rely on gene knockouts and that lead to medicines without toxic side
effects. Therefore, certain moonlighting proteins, such as those involved in macro-
molecular ultrastructures and in metabolic and signaling pathways, are potentially
attractive targets for drug therapies. This is because it may be possible to find drugs
that inhibit their pathological but not their physiological functions hence with very
limited, toxic effects.
Search WWH ::
Custom Search