Teneurins are a family of

phylogenetically In biology, phylogenetics (; from Greek φυλή/ φῦλον [] "tribe, clan, race", and wikt:γενετικός, γενετικός [] "origin, source, birth") is the study of the evolutionary history and relationships among or within groups o ...

conserved single-pass transmembrane glycoproteins expressed during pattern formation and morphogenesis. The name refers to "ten-a" (from " tenascin-like protein, accessory") and "

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

", the primary site of teneurin expression. Ten-m refers to tenascin-like protein major. Teneurins are highly conserved between ''Drosophila'', ''C. elegans'' and vertebrates. In each species, they are expressed by a subset of neurons as well as at sites of pattern formation and morphogenesis. In ''Drosophila'', a teneurin known as ten-m or Odz is a pair-rule gene, and its expression is required for normal development. The knockdown of teneurin (''ten-1'') expression in ''C. elegans'' with RNAi leads to abnormal neuronal pathfinding and abnormal development of the gonads. The intracellular domain of some, if not all, teneurins can be cleaved and transported to the

cell nucleus The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, h ...

, where it proposed to act as a transcription factor. A peptide derived from the terminus of the extracellular domain shares structural homology with certain neuropeptides. There are four teneurin genes in vertebrates, named teneurin-1 through -4. Other names found in the literature include Odz-1 through -4 and Tenm-1 through -4.

History

Originally discovered as ten-m and ten-a in '' Drosophila melanogaster'', the teneurin family is conserved from ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...

'' (''ten-1'') to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct protein domain architecture is

highly conserved In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...

between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and ''

C. elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

'' TEN-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.

Function

Teneurins translocate to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

where they regulate transcriptional activity. Teneurins promote neurite outgrowth and

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

. The intracellular domain interacts with the DNA-binding transcriptional

repressor In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the ...

s and also regulate the activity of transcription factors. Additionally, they have been known to interact with the cytoskeleton adaptor protein, CAP/ponsin, suggesting cell signalling roles and regulation of actin organisation. Teneurin-3 regulates the structural and functional wiring of retinal ganglion cells in the vertebrate visual system.

Structure

Ten-m1–4, exist as homodimers and undergo homophilic interactions in vertebrates.

C terminal domain

The large C-terminal extracellular domain consists of eight EGF-like

repeat Repeat may refer to: * Rerun, a rebroadcast of an episode of a radio or television program * Repeated sequence (DNA), a pattern of nucleic acid (DNA or RNA) that occurs in multiple copies throughout the genome ** CRISPR * The smallest rectangle ...

s (se
PROSITEDOC
, a region of conserved

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

s and unique YD-repeats.

N terminal domain

The teneurin intracellular (IC) domain (∼300–400 aa) is located at the N-terminus and contains a number of conserved putative tyrosine

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

sites, two EF-hand-like calcium-binding motifs, and two polyproline domains. These

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

-rich stretches are characteristic of SH3-binding sites. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins. This domain is found in the intracellular N-terminal region of the teneurin family.

Human genes

Human genes encoded teneurin domain proteins (TENM1-4) are list in the infoboxes.