The concept of homeoprotein transduction as a novel signaling pathway has dramatically evolved since it was
first proposed in 1991. It is now well established in several biological systems from plants to mammals. In this review, the
different steps that have led to this unexpected observation are recalled and the developmental and physiological models
that have allowed us (and a few others) to consolidate the original hypothesis are described. Because homeoprotein signaling
is active in plants and animals it is proposed that it has predated the separation between animals and plants and is thus
very ancient. This may explain why the basic phenomenon of homeoprotein transduction is so minimalist, requiring no
specific receptors or transduction pathways beside those offered by mitochondria, organelles present in all eukaryotic
cells. Indeed complexity has been added in the course of evolution and the conservation of homeoprotein transduction is
discussed in the context of its synergy with bona fide signaling mechanism that may have added robustness to this primitive
cell communication device. The same synergy possibly explains why homeoprotein signaling is important both in
embryonic development and in adult functions fulfilled by signaling entities (e.g. growth factors) themselves active
throughout development and in the adult. The cell biological mechanism of homeoprotein transfer is also discussed. Although
it is clear that many questions are still in want of precise answers, it appears that the sequences responsible both
for secretion and internalization are in the DNA-binding domain and very highly conserved among most homeoproteins.
On this basis, it is proposed that this signaling pathway is likely to imply as many as 200 proteins that participate in a
myriad of developmental and physiological pathways.
Keywords: Homeoproteins, Signaling, Development, Morphogenesis, Nervous System, Plasticity.
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Published on: 31 August, 2013
Page: [361 - 370]