Identification, Evolution and Expression of an Insulin-Like Peptide in the Cephalochordate Branchiostoma lanceolatum

Abstract

Insulin is one of the most studied proteins since it is central to the regulation of carbohydrate and fat metabolism in vertebrates and its expression and release are disturbed in diabetes, the most frequent human metabolic disease worldwide. However, the evolution of the function of the insulin protein family is still unclear. In this study, we present a phylogenetic and developmental analysis of the Insulin Like Peptide (ILP) in the cephalochordate amphioxus. We identified an ILP in the European amphioxus Branchiostoma lanceolatum that displays structural characteristics of both vertebrate insulin and Insulin-like Growth Factors (IGFs). Our phylogenetic analysis revealed that amphioxus ILP represents the sister group of both vertebrate insulin and IGF proteins. We also characterized both temporal and spatial expression of ILP in amphioxus. We show that ilp is highly expressed in endoderm and paraxial mesoderm during development, and mainly expressed in the gut of both the developing embryo and adult. We hypothesize that ILP has critical implications in both developmental processes and metabolism and could display IGF- and insulin-like functions in amphioxus supporting the idea of a common ancestral protein.

Developmental cell-cell communication pathways in the cephalochordate amphioxus: actors and functions

“…Ilp Insulin, IGF1, IGF2 (Guo et al, 2009, Holland et al, 1997, Lecroisey et al, 2015 Insulin, IGF1, IGF2 PD/VEGFR Receptor PD/VEGFR PDGFRA, PDGFRB, FLT3, CSF1R, KIT, VEGFR1, VEGFR2, VEGFR3 (Pascual-Anaya et al, 2013) TRK Receptor Trk NTRK1, NTRK2, NTRK3 (Benito-Gutierrez et al, 2005) Ligand NT NGF, BDNF, NT-3, NT-4 all RTKs Others AKT AKT1, AKT2, AKT3 (Bertrand et al, 2009) PDK PDK (Bertrand et al, 2009) PLCγ PLCγ1, PLCγ2 (Bertrand et al, 2009) PKCα/β/γ PKCα, PKCβ, PKCδ (Bertrand et al, 2009) RAF RAF1, ARAF, BRAF (Bertrand et al, 2009) H/K/NRASa HRAS, NRAS, KRAS (Bertrand et al, 2009)…”

“…Two genes, coding for Insulin-like peptides (ILP) were described in the genome of B. floridae (Lecroisey et al, 2015) long after the first description of an Ilp gene in B. californiensis (Chan et al, 1990). Both are ohnologues of vertebrate insulin genes IGF1 and IGF2.…”

The role of a new insulin-like peptide in the pearl oyster Pinctada fucata martensii

“…1). Previous studies showed that the insulin-relaxin superfamily have a similar modular organisation as their precursor, including an N-terminal signal peptide, A, B and C domains 2,13 . Post-translational modification leads to cleavage of the signal peptide and the C-peptide, resulting in a mature hormone consisting of the A and B chains.…”

“…These proteins exhibit a highly structural conservation. They share conserved cysteine residues required for the formation of disulphide bridges which are the hallmark of this superfamily 2 . The insulin-relaxin superfamily has a variety of functions; they can activate both PI3K/AKT and MAPK pathways that are composed of multiple effectors 3 .…”

“…Insulin is a key peptide hormone that can activate the PI3K and MAPK pathways to regulate metabolism and growth in metazoans 1,[7][8][9] . In vertebrates, the function of insulin has been extensively studied since it is central to regulate the glycogen, fat, and protein metabolism 2,10,11 .…”