Cell biology of osteoclasts II: PSTP1, an adaptor of protein tyrosine phosphatases, as a major component controlling of actin and sealing zone dynamics during bone degradation

• Applicant: Professor Dr. Bernard Hoflack
• Subject Area: Cell Biology
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 204054066

To digest bone, osteoclasts need to adhere onto its surface, to build up a sealing zone by reorganizing their actin-rich podosomes into tight belts. These events are controlled by the Src tyrosine kinase, Using quantitative proteomics, we have previously identified the proline-serine-threonine phosphataseinteracting protein 1 (PSTPIP1) as a Src substrate. Our working hypothesis is that PSTPIP1 binds to podosomes via its F-BAR domain where it recruits via its SH3 domain PEST-protein tyrosine phosphatases, which could then inactivate key components of podosomes thereby destabilizing sealing zones. To comprehensively understand PSTPIP1 function in osteoclasts, it will be necessary 1. To understand how PSTPIP1 is recruited onto podosomes and how its activity is regulated, 2. To identify its interacting partners, in particular specific protein tyrosine phosphatases and 3. To identify the substrates of these phosphatases, which are likely key structural and regulatory components of sealing zone dynamics. The project will combine quantitative proteomic analyses and functional studies based on videomicroscopy applied to siRNA treated osteoclasts.

• DFG Programme: Research Grants