Periodic Reporting for period 4 - APOLs (Role of Apolipoproteins L in immunity and disease)
Période du rapport: 2020-03-01 au 2021-06-30
In 2010 we discovered that many human individuals in Africa possess mutations in their APOL1 gene, termed G1 and G2, which enable them to resist infection by Trypanosoma rhodesiense. However, this benefit goes with a cost, as these individuals exhibit a strong probability to develop chronic kidney disease, particularly linked with viral infection.
Based on our findings regarding the effect of APOL1 on trypanosomes as well as the structure and expression characteristics of this family of proteins, notably the strong increase of APOLs expression under inflammatory conditions, we suspected APOLs to play a role in the control of the cell fate in the immune system. Therefore, we have proposed to study this role and to decipher the mechanism by which APOL1 variants cause kidney disease. In this work, we made the totally unexpected discovery that APOL1 and APOL3 are involved in the control of the podocyte cytoskeleton, through their ability to regulate the fission and fusion of intracellular membranes. Therefore, our research revealed novel aspects regarding the processes affecting cellular dynamics such as secretion, exocytosis and autophagy, not only in podocytes but also in other cell types.
I believe that understanding the function of APOLs is important for society, because the molecular mechanisms of chronic kidney disease are not known. Moreover, as proposed in my 2021 review on the role of APOLs, these proteins could also play an important role in neurotransmission diseases and cancer.