Cells are highly complicated in their structure and molecular interactions. Understanding the interactions between proteins is key in finding cures for diseases such as cancers and inflammatory and cardiovascular diseases. The intracellular structural protein network is connected through membrane receptors (such as integrins) to the outside environment. The majority of our cells are surrounded by extracellular protein networks (extracellular matrix; ECM). When integrins bind to their ligands, they activate signalling pathways involved in many cellular processes such as cell movement, invasion and survival. Misbalance in the integrin signalling pathways may lead to severe human pathologies and diseases.
Today, many integrin ligands have been identified, which have an important role in cell behaviour. One of the proteins that directly interacts with integrin is called talin. Humans have two talin genes called talin1 and talin2.
“Talin1 is widely expressed in almost all tissues: mostly in the kidney, liver, spleen, stomach, lung, and vascular smooth muscles. In contrast, talin 2 is dominantly expressed in the heart, brain, and skeletal muscle. Previous studies have shown that if the talin1 gene is taken from mouse embryos it is lethal, but this was not observed for the talin2 gene. My doctoral thesis focuses almost solely on Talin1”, explains MSc Latifeh Azizi.
Talin is a large cytoplasmic protein that directly interacts with integrins. As integrins are central for numerous cellular processes, any disturbance in talin structure, such as point mutation, can have serious consequences on cell fate and the whole tissue. There are only a few studies, which directly link talin to diseases, but previous investigations have shown the presence of talin in the serum of patients with different diseases such as hepatocellular carcinoma and spontaneous artery dissection disease. Therefore, talin appears as a potential biomarker for the early detection of the diseases.
“For my dissertation study, we studied the structure of the talin head using bioinformatic, biochemical and cell culture methods and found an additional role for the structurally flexible polypeptide segment in the talin F1 domain, which was found essential for integrin activation. In addition, I have screened a human cancer database in which talin point mutations have been associated with various cancers. We observed that a single missense mutation can have a drastic effect on cell behaviour leading to severely disturbed cell functions, including slower cell migration and spreading, which are vital for normal cell function,“ Azizi says.
Public defence on Friday 18 August
The doctoral dissertation of MSc Latifeh Azizi in the field of cell and molecular biology titled Structure-function of Talin1; An integrin adaptor protein involved in health and disease will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12.00 o’clock on Friday 18 August 2023 at Kauppi campus, auditorium F114 (Arvo Ylpön katu 34). The Opponent will be Professor Aki Manninen from the University of Oulu. The Custos will be professor Vesa Hytönen from the Faculty of Medicine and Health Technology.
The doctoral dissertation is available online.
The public defence can be followed via a remote connection.
Photo: Sofia Azizi