Abstract
The existence of the teneurin C-terminal associated peptides (TCAP) was reported in 2004 after screening a rainbow trout hypothalamic cDNA for corticotropin-releasing factor (CRF)-related homologs. In vertebrates, there are four TCAP paralogs, where each peptide is associated with a teneurin transmembrane protein. The TCAPs are 40 or 41 amino acids in length and possess less than 20% residue identity with the CRF family of paralogs. Orthologs of TCAP are found in all metazoans with the possible exception of poriferans and cnidarians. Recent evidence indicates that TCAP and the teneurins may have been introduced into the Metazoa via horizontal gene transfer from prokaryotes into a basal protistan. Thus, the origin of the TCAPs likely predated that of the CRF family. In the mammalian brain, TCAP-1 is transcribed independently from teneurin-1. Moreover, TCAP-1 acts on neurons by a CRF-receptor independent signal transduction pathway to regulate cellular cytoskeletal function to stimulate cell activity. Administration of synthetic TCAP-1 to rodents inhibits a number of CRF- and stress-associated behaviors via a hypothalamic–pituitary–adrenal (HPA) axis-independent mechanism.
Highlights
Corticotropin-releasing factor (CRF) is part of an evolutionary conserved peptide family integral to the regulation of stressassociated behavior and physiology in metazoans
terminal associated peptides (TCAP) was originally identified in a rainbow trout cDNA library screen for potential CRF homologs and share a number of structural similarities with the CRF family of peptides, they have less than 20% sequence similarity to the CRF family (Qian et al, 2004; Lovejoy et al, 2006)
Chick, and rodents indicate that expressed throughout the brain, TCAP-1 is concentrated in the limbic regions including the hippocampus, hypothalamus, and amygdala (Wang et al, 2005; Tan et al, 2009, 2011). It is in the rat hippocampus and amygdala that TCAP-1 has been shown to exert its neuromodulatory effects on behavior and stress
Summary
Corticotropin-releasing factor (CRF) is part of an evolutionary conserved peptide family integral to the regulation of stressassociated behavior and physiology in metazoans. Early-evolving gene systems integral to the survival of an organism are evolutionarily selected for, and because of this, may give rise to additional paralogous lineages via gene, genomic, and chromosomal duplication events. Such early evolving systems will likely become associated with newer evolving molecular and physiological systems. Because of the evolutionary age of the CRF system, it is likely that it is modulated, in turn, by even earlier evolving systems One such candidate for an early evolving CRF-modulatory system may be represented by TCAP-1, a member of the teneurin C-terminal-associated peptides family. The presence of CRF orthologs in arthropods indicates that the earliest CRF-like www.frontiersin.org
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