Keynote Conference - Interevent

L#19
Regulation of insect metamorphosis and the role of
microRNAs. Nepenthe teams up with Psyche
Xavier Bellés
Institute of Evolutionary Biology (CSIC-UPF), Barcelona
E-mail: xavier.belles@ibe.upf-csic.es
Insect metamorphosis has fascinated mankind since the time of
Aristotle, some two thousand years ago. But it was not until
the decade of 1930 that the studies of Vincent B. Wigglesworth
showed that insect metamorphosis is regulated by two
hormones: the molting hormone, which induces the successive
molts, and the juvenile hormone, which maintains the juvenile
character of them. Then, a number of transcription factors act
as mediators of these hormones, as well as a number of target
genes that codify for proteins, giving the shape and behaviour
of a juvenile or an adult stage. Working on the cockroach
Blattella germanica, we found that microRNAs, which are RNAs
of ca. 22 nucleotides that play a repressing action on mRNA,
have a key role in metamorphosis. We silenced the expression
of dicer-1 (a ribonuclease that mediates the maturation of
microRNAs) in the last nymphal instar and the cockroaches,
instead of molting to the adult stage, transformed into
supernumerary nymphs. We presume that there are
microRNAs that repress the expression of genes that maintain
the juvenile status quo (like Nepenthe, the drug of
forgetfulness of the Greeks). This leads to a change of genetic
program, from juvenile to adult and, within the latter, there
must be other microRNAs that modulate and refine the
expression of genes that give rise to the adult animal, thus
making it all right (like Psyche, the Greek symbol of
transformation and new life).
L#20
The prion protein as a prototypical cell surface scaffold protein.
Rafael Linden
Instituto de Biofísica da UFRJ, Rio de Janeiro, Brazil.
Based on multiple interaction partners and pleiotropic signaling
properties, we proposed the hypothesis that the prion protein
(PrPC) is a cell surface scaffold protein, that serves as a dynamic
platform for the assembly of signaling modules involved in
widespread systemic functions. Our recent work is focused on 3
topics: (a) identification and validation of additional molecular
interactions of PrPC; (b) structural evidence for allosteric
function of PrPC; (c) functional properties and dysfunction of
PrPC beyond the nervous system. A phage display screen,
together with evidence from PrPC-null mice, implicate several
neurotransmitter receptors and/or transporters in PrPCdependent
signaling; Biophysical techniques showed that
interaction of PrPC with its ligand hop/STI1 entails reciprocal
structural remodeling, and strongly suggest allosteric effects
that may be involved in the propagation of signals through PrPCmediated
multiprotein complexes; Beyond the nervous system,
we found that both peripheral inflammation and behavioral
stress modulate the content of PrPC at the plasma membrane of
neutrophils, with consequences upon peroxide-dependent
cytotoxicity towards vascular endothelial cells. Our studies add
to the understanding of both allosteric properties of the prion
protein and systemic control of its expression and function. The
data are consistent with the scaffold hypothesis that explains
the multiple roles of the prion protein in physiology and
pathology, and further suggest that PrPC may be relevant for
clinically observed associations of stress and anxiety with either
the severity or the progression of various degenerative/
noncommunicable diseases.
(Supported by CNPq, FAPERJ, CAPES, FAPESP)
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