Teneurins are a family of

phylogenetically In biology, phylogenetics () is the study of the evolutionary history of life using observable characteristics of organisms (or genes), which is known as phylogenetic inference. It infers the relationship among organisms based on empirical data ...

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

glycoproteins Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

expressed during

pattern formation The science of pattern formation deals with the visible, (statistically) orderly outcomes of self-organization and the common principles behind similar patterns in nature. In developmental biology, pattern formation refers to the generation of c ...

and

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of deve ...

. The name refers to "ten-a" (from "

tenascin Tenascins are extracellular matrix glycoproteins. They are abundant in the extracellular matrix of developing vertebrate embryos and they reappear around healing wounds and in the stroma of some tumors. Types There are four members of the tena ...

-like protein, accessory") and "

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

", the primary site of teneurin expression. Ten-m refers to tenascin-like protein major. Teneurins are highly conserved between ''Drosophila'', ''C. elegans'' and

vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

. 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 (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

, where it proposed to act as a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

. A peptide derived from the terminus of the extracellular domain shares structural homology with certain

neuropeptides Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

. 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 ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

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 Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...

'' (''ten-1'') to vertebrates, in which four

paralog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

s exist (teneurin-1 to -4 or odz-1 to -4). Their distinct

protein domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...

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 Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordata, chordate s ...

and

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

teneurins, particularly in the

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

part. The

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

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'' ( ...

'' 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

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s 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 Nucleu ...

where they regulate transcriptional activity. Teneurins promote

neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...

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_junction, cell junc ...

. 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

s. 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 A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina ...

in the vertebrate

visual system The visual system is the physiological basis of visual perception (the ability to perception, detect and process light). The system detects, phototransduction, transduces and interprets information concerning light within the visible range to ...

Structure

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

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 th ...

s (se
PROSITEDOC
, a region of conserved

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

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 -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

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 p ...

-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

s. 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.