Role of the teneurins, teneurin C-terminal associated peptides (TCAP) in reproduction: clinical perspectives

Abstract

In humans, the teneurin gene family consists of four highly conserved paralogous genes that are the result of early vertebrate gene duplications arising from a gene introduced into multicellular organisms from a bacterial ancestor. In vertebrates and humans, the teneurins have become integrated into a number of critical physiological systems including several aspects of reproductive physiology. Structurally complex, these genes possess a sequence in their terminal exon that encodes for a bioactive peptide sequence termed the 'teneurin C-terminal associated peptide' (TCAP). The teneurin/TCAP protein forms an intercellular adhesive unit with its receptor, latrophilin, an Adhesion family G-protein coupled receptor. It is present in numerous cell types and has been implicated in gamete migration and gonadal morphology. Moreover, TCAP is highly effective at reducing the corticotropin-releasing factor (CRF) stress response. As a result, TCAP may also play a role in regulating the stress-associated inhibition of reproduction. In addition, the teneurins and TCAP have been implicated in tumorigenesis associated with reproductive tissues. Therefore, the teneurin/TCAP system may offer clinicians a novel biomarker system upon which to diagnose some reproductive pathologies.

Subphenotype meta-analysis of testicular cancer genome-wide association study data suggests a role for RBFOX family genes in cryptorchidism susceptibility

“…1 and Table II), although the mapped intragenic signals varied among them (Supplementary Table SII). The 19 shared genes include the paralogs RBFOX1 and RBFOX3, which encode RBPs targeting (U)GCAUG nucleotide motifs within developmental neural transcripts and TENM2 and TENM4, encoding teneurins, which function in neuronal, gonadal and sensory pathway development through regulation of cytoskeletal organization (Lovejoy and Pavlovic, 2015;Woelfle et al, 2015). Suggestive intragenic signals were also present in at least 4 of the 6 UDT subphenotype analyses for ADAMTSL1, CNTN4, CSMD1, DNAH11, ERG, FHIT, LOC105377441, PTPRD and RBFOX1.…”

Genomic analyses identify signaling pathways and biological processes in small and large melanoma

“…Interestingly, the CLOCK and BMAL1 can activate RHOA to drive the F-actin formation in cancer cells 54 . TCAP has been implicated in the progression of tumor-associated with reproductive tissues 55 .…”

A Putative Role of Teneurin-2 and Its Related Proteins in Astrocytes

“…Teneurins are primarily involved with neuronal migration, axonal guidance, as well as formation, differentiation and maintenance of synapses in the CNS (Mosca, 2015; Antinucci et al, 2016). Previous studies have also correlated these proteins with mental disorders, congenital diseases and some types of tumors (Vinatzer et al, 2008; Ziegler et al, 2012; Boeva et al, 2013; Heinrich et al, 2013; Nakaya et al, 2013; Ivorra et al, 2014; Zhang et al, 2014; Bastías-Candia et al, 2015; Hor et al, 2015; Lovejoy and Pavlović, 2015; Schöler et al, 2015; Vater et al, 2015; Alkelai et al, 2016; Cheng et al, 2017; Graumann et al, 2017; Talamillo et al, 2017). Interestingly, teneurins contain a cleavage site in their carboxyl terminal that originates fragments of 40 to 41 amino acids, named teneurin C-terminal-associated peptides (TCAP-1-4), which show structural similarities to corticotrophin-releasing factor (CRF) (Qian et al, 2004; Wang et al, 2005; Lovejoy et al, 2006).…”