Tensin was first identified as a 220 kDa multi-domain
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
localized to the specialized regions of
plasma membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
called integrin-mediated
focal adhesions
In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More p ...
(which are formed around a transmembrane core of an αβ integrin heterodimer).
Genome sequencing and comparison have revealed the existence of four tensin genes in humans.
These genes appear to be related by ancient instances of gene duplication.
Tensin binds to
actin
Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...
filaments and contains a
phosphotyrosine-binding (PTB) domain at the C-terminus, which interacts with the cytoplasmic tail of β integrins. These interactions allow tensin to link actin filaments to integrin receptors. Several factors induce tyrosine phosphorylation of tensin. Thus, tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins.
Haynie, by contrast, argues in a review of tensin structure and function that experimental evidence for the specific association of tensin with
actin
Actin is a protein family, family of Globular protein, globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in myofibril, muscle fibrils. It is found in essentially all Eukaryote, eukaryotic cel ...
filaments is inconclusive at best.
Recent work has also demonstrated TNS3 and TNS4 to exhibit force-dependent recruitment to keratin network in epithelial cells, highlighting its novel role in mechanotransduction.
It is beyond reasonable doubt, however, that tensin 1, tensin 2 and tensin 3 each contains a
protein tyrosine phosphatase
Protein tyrosine phosphatases (EC 3.1.3.48, systematic name protein-tyrosine-phosphate phosphohydrolase) are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins:
: proteintyrosine phosphate + H2O = ...
(PTP) domain near the N-terminus. The PTP domain is unlikely to be active in tensin 1, owing to mutation of the essential nucleophilic cysteine in the signature motif to asparagine.
Nevertheless,
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase, the well-studied tumor suppressor that is better known as
PTEN, gets its name from homology with PTPs and tensin 1.
More detailed structure comparisons have revealed that tensins 1-3,
PTEN,
auxilin and other proteins in animals, plants and fungi comprise a PTP-C2 superdomain. An integrated PTP domain and
C2 domain
A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. The typical version (PKC-C2) has a beta-sandwich composed of 8 β-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by ...
, the PTP-C2 superdomain came into existence over 1 billion years ago and has functioned as a single heritable unit since then.
The first tensin
cDNA
In genetics, complementary DNA (cDNA) is DNA synthesized from a single-stranded RNA (e.g., messenger RNA (mRNA) or microRNA (miRNA)) template in a reaction catalyzed by the enzyme reverse transcriptase. cDNA is often used to express a speci ...
sequence was isolated from chicken.
Analysis of knockout mice has demonstrated critical roles of tensin in renal function, muscle regeneration, and cell migration. Evidence is now emerging to suggest tensin is an important component linking the ECM, the actin cytoskeleton, and signal transduction. Therefore, tensin and its downstream signaling molecules may be targets for therapeutic interventions in renal disease, wound healing and cancer.
References
{{Reflist
External links
MBInfo - Tensin in Cell AdhesionTensin review2014 tensin review
Proteins