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Publication : Selective binding and transport of protocadherin 15 isoforms by stereocilia unconventional myosins in a heterologous expression system.

First Author  Ballesteros A Year  2022
Journal  Sci Rep Volume  12
Issue  1 Pages  13764
PubMed ID  35962067 Mgi Jnum  J:345076
Mgi Id  MGI:7331133 Doi  10.1038/s41598-022-17757-0
Citation  Ballesteros A, et al. (2022) Selective binding and transport of protocadherin 15 isoforms by stereocilia unconventional myosins in a heterologous expression system. Sci Rep 12(1):13764
abstractText  During hair cell development, the mechanoelectrical transduction (MET) apparatus is assembled at the stereocilia tips, where it coexists with the stereocilia actin regulatory machinery. While the myosin-based tipward transport of actin regulatory proteins is well studied, isoform complexity and built-in redundancies in the MET apparatus have limited our understanding of how MET components are transported. We used a heterologous expression system to elucidate the myosin selective transport of isoforms of protocadherin 15 (PCDH15), the protein that mechanically gates the MET apparatus. We show that MYO7A selectively transports the CD3 isoform while MYO3A and MYO3B transports the CD2 isoform. Furthermore, MYO15A showed an insignificant role in the transport of PCDH15, and none of the myosins tested transport PCDH15-CD1. Our data suggest an important role for MYO3A, MYO3B, and MYO7A in the MET apparatus formation and highlight the intricate nature of MET and actin regulation during development and functional maturation of the stereocilia bundle.
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