Tensin proteins are a family of intracellular molecules that act as molecular bridges within cellular structures. They play diverse roles in various biological processes, helping cells maintain their shape, move, and communicate with their surroundings. Understanding tensins provides insight into the proper functioning of tissues throughout the body.
Cellular Foundation of Tensin
Tensin proteins are primarily located at specialized structures within cells known as focal adhesions. Focal adhesions serve as physical connections that link the internal framework of a cell, specifically its actin cytoskeleton, to the extracellular matrix (ECM) outside the cell. This linkage provides both structural support and channels for communication between the cell and its environment. Tensin proteins contain multiple domains, including Src Homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which allow them to interact with various other proteins and signaling molecules.
The mammalian tensin family consists of four distinct members: Tensin1 (TNS1), Tensin2 (TNS2), Tensin3 (TNS3), and Tensin4 (TNS4), also known as C-terminal tensin-like (CTEN). These family members share considerable structural similarities and contribute to the molecular linkage between the ECM and the cytoskeletal networks. Tensin proteins facilitate the assembly and disassembly of signaling complexes at focal adhesions by recruiting phosphotyrosine-containing proteins and providing interaction sites for other SH2-containing proteins. This dynamic interaction allows tensins to integrate mechanical cues from the environment with internal cellular responses.
Tensin’s Diverse Biological Roles
Tensin proteins play broad roles in maintaining cellular function and tissue integrity. They are involved in cell adhesion, the process by which cells stick to each other and their environment, which is fundamental for forming organized tissues. Tensin proteins also contribute to cell migration, the directed movement of cells important for embryonic development, wound healing, and immune responses.
Specific tensin family members contribute to these processes through distinct mechanisms. For instance, TNS1 promotes cell migration by interacting with DLC1, which helps regulate cell movement, and by linking certain phosphorylated proteins to the actin cytoskeleton. TNS1, TNS2, and TNS3 are also involved in the internalization of active integrins, which is necessary for the dynamic turnover of focal adhesions and efficient cell migration. Tensin proteins also participate in signal transduction, allowing cells to receive and interpret external cues and respond accordingly.
Beyond migration and adhesion, tensins contribute to cell proliferation, the process of cell growth and division. TNS1 can promote cell proliferation by activating certain signaling pathways, while TNS2 negatively regulates it by suppressing others. TNS3 and TNS4 also influence cell proliferation by affecting proteins that control the cell cycle. Tensins are also recognized for their role in mechanical sensing, allowing cells to respond to changes in environmental stiffness. For example, TNS1 can adjust its protein turnover rate in response to substrate stiffness, influencing cell attachment and migration.
Tensin’s Impact on Health and Disease
Dysregulation or mutations in tensin proteins can have significant implications for human health. Tensins are recognized for their roles in maintaining normal tissue structures, particularly in the kidney and heart. Deficiencies in TNS1 or TNS2 have been linked to chronic kidney diseases, including cystic kidneys and nephrotic syndrome. Molecular pathways involved in these kidney defects include the Mek/Erk pathway in TNS1-deficient mice and the PI3K/Akt/mTORC1 pathway in TNS2 mutant mice.
Tensin proteins also have a complex involvement in various types of cancer. Their expression levels can vary significantly in cancerous tissues, sometimes acting as tumor suppressors and other times promoting cancer cell metastasis. For instance, all four tensin genes are significantly downregulated in human kidney tumors compared to normal kidney tissue, with reductions ranging from 50% to 100%. This general loss of tensins in the kidney may facilitate tumor development and spread.
TNS3, in particular, has been identified as a negative regulator of cell migration and invasion, with its stable expression inhibiting these processes in kidney cells. Conversely, a reduction in TNS3 expression can lead to increased cell migration. In breast cancer, TNS1 has been shown to influence metastasis, with high expression correlating with prolonged survival without distant metastases. However, TNS4 can promote cell migration and invasion in some cancers, such as colorectal cancer, by influencing signaling pathways.