The Insulin receptor pathway

Insulin/IGF-1 signaling (IIS) regulates key physiological processes in Metazoa: metabolism, growth, cell proliferation, reproduction, longevity or cancer. In vertebrates, insulin and IGFs regulate these processes by binding to Insulin and IGF-1 Receptors and the activation of their cellular signaling pathways. In insects, by contrast, a large number of insulin-like peptides (ILP) bind to fewer receptors. How do these peptides and their receptors regulate the different processes in which they are involved? Are they functionally redundant or have specific functions? Answering this question will provided relevant information about a new mode of action of such an important signaling pathway.

In the German cockroach, Blattella germanica, we have identified 8 ILPs, which are differently expressed in the tissues, and respond differently to the nutritional status. In addition, recent studies have demonstrated that, although most insects have two insulin receptors (InR), the evolutionary lineage that gave rise to cockroaches, termites and stick insects, acquired a third InR by gene duplication.

Our research projects analyze what are the processes in which this signaling pathway is involved and which are the specific functions of each of the three InRs (InR1, 2 and 3) and of the ILPs that are their ligands. Previous results indicated that InR2 is involved in the activation of juvenile hormone synthesis in adult females as well as in the growth of the later nymphal stages.

The identification of the functions of the three InR will determine the outcome of the copies that appeared after the duplication, which could be: non-functionalization, subfunctionalization or neofunctionalization.

RNAi mode of action

The RNA Interference (RNAi) methodology takes advantage of the mechanisms developed by the cells to defend themselves against the attack of harmful agents, such as certain types of viruses or transposons. Thus, treatment with a dsRNA homologous to a given mRNA will specifically knock down this mRNA and, consequently, the encoded protein. In our lab, we are interested in understanding how RNAi works in insects for producing the RNA knock down effect. The study involves the analysis of the characteristics of the dsRNA molecules for producing the maximum effect, how Dicer or Argonaute enzymes contribute to the knock down and which intermediary molecules (small interfering RNAs) are more propitious to be produced.  

Insect neuropeptides

Neuropeptides constitute the largest group of bioactive chemical messengers described in metazoans. This is possible because they are chains of amino acids, which allows an almost unlimited variety of sequences. Besides being very different structurally, peptides are very versatile messengers, acting as hormones or neurohormones (when released into the circulation from endocrine glands or neurosecretory cells), as neurotransmitters (when produced by neurons and released at a synapse) or as neuromodulators (when they are released into the synaptic gap to modulate the action of a neurotransmitter).

In insects, neuropeptides are involved in most physiological and developmental processes, such as growth, molting, metamorphosis, reproduction, diapause, food intake, metabolism, etc. In our group we have spent years studying the structure and function of insect neuropeptides related to different physiological processes.