Teneurin C-terminal associated peptides (TCAP): modulators of corticotropin-releasing factor (CRF) physiology and behavior

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.

The Mechanism of Regulated Release of Lasso/Teneurin-2

“…MS analysis of the native Lasso fragments (Figure 7E ) revealed a large number of peptides from the ectodomain, including the peptide (MW 3469.95, see above) localized immediately downstream of the S1 (furin) site, but no peptides from the other Lasso domains. Two tryptic peptides were found within the sequence corresponding to TCAP, which indicated that at least the larger of the two NF (NF268) was not cleaved at the C-terminus, contrary to what was proposed previously for teneurin-2 (Chen et al, 2013 ).…”

On the Teneurin track: a new synaptic organization molecule emerges

“…Application of the Teneurin-2 C-terminus in hippocampal culture induces presynaptic Ca 2+ signaling (Silva et al, 2011 ). This is reminiscent of the Teneurin C-terminal associated peptide (TCAP), a 41-residue peptide that can be liberated and is thought to regulate stress response, dendritic remodeling in the hippocampus, BDNF levels, and corticotropin-releasing factor signaling (Rotzinger et al, 2010 ; Ng et al, 2012 ; Tan et al, 2012 ; Chen et al, 2013 ). Indeed, Teneurin-2 can be cleaved in culture (Silva et al, 2011 ), supporting this model but could also function by another, unknown mechanism.…”

Energy Metabolism and Behavior in the Corticotropin-Releasing Factor Family of Peptides

“…In their contribution, Chen et al (2013) examine the evolutionary origins of the tenuerin C-terminal associated peptides (TCAP), peptides which may have predated the origin of the CRF peptide family. Chen et al (2013) review data on the neuromodulatory actions of TCAP-1 and both its direct and indirect effects as an indirect modulator of CRF intracellular signaling.…”

“…In their contribution, Chen et al (2013) examine the evolutionary origins of the tenuerin C-terminal associated peptides (TCAP), peptides which may have predated the origin of the CRF peptide family. Chen et al (2013) review data on the neuromodulatory actions of TCAP-1 and both its direct and indirect effects as an indirect modulator of CRF intracellular signaling.Feeding and intake of nutrients is essential for the success of any species. A stress-response, as regulated by the CRF family of peptides, generally has suppressive actions on appetite and digestion in order to shunt energy from a parasympathetic need to arousal and sympathetic requirements.…”