Description
Collagen maturation (through post-translational modifications, quaternary assembly and transport) is critical for tissue and organ development and homeostasis. This complex process involves numerous actors in different subcellular compartments, which in turn depend on highly regulated trafficking systems. Although the mechanisms of vesicular trafficking, membrane tethering and fusion are conserved throughout eukaryotic evolution, highly specialized tethering complexes have evolved to regulate specific fusion events. Recently, a novel pathway regulating collagen trafficking has been identified. Central to this pathway are two trafficking proteins, homologous to, but not part of, classical vesicle tethering components. At present, very little is known about their specific functions. Genetic mutations in both proteins induce rare but highly invalidating and often lethal phenotypes, characterized by abnormal collagen distribution, disorders of extracellular-matrix organization and impairment in endosomal trafficking. In this project, a multidisciplinary approach merging cutting-edge affinity purification coupled to mass spectrometry with structural biology and biophysics was developed to decipher the molecular mechanisms driving membrane tethering and, more broadly, endosomal trafficking through this new complex. These results unveil unprecedented mechanisms of vesicular trafficking, offering potential for translational research on collagen-related diseases and disorders related to vesicular trafficking, and may pave the way to future therapeutic strategies.
Role of our laboratory
Our laboratory hosted Dr Antonella Chiapparino, PI of the COTETHERS project, and synergistically developed the project focusing on collagen PTM enzymes and chaperones and developing new technologies for protein identification, characterization and recombinant production.
Project details
- Full title: Molecular characterization of vesicle tethering complexes as novel regulators of collagen trafficking
- Funding agency: European Commission
- Programme: H2020-MSCA-IF-2016
- Project code: 745934
- Total project funding: EUR 168’277.20
- Project period: 1 April 2017 – 31 March 2019
- Institutions involved: University of Pavia (Italy)
